bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the Role of Pikfyve in Modulating ER Functions/Dynamics and ER-Lysosome Contact Sites
Authors: Adamji Zainab
Published: September 2024

Lysosomes are the major degradative organelle in the cell. Their degradative function is integrated with physiological functions like nutrient sensing, metabolic regulation, and cholesterol transport. The lipid kinase PIKfyve regulates lysosome function. Loss of PIKfyve activity causes several defects including lysosome coalescence. Lysosomes form membrane contact sites (MCSs) with other organelles like the endoplasmic reticulum (ER), which facilitates protein and lipid synthesis. MCSs modulate signalling processes and organelle remodelling. ER-lysosome contacts are implicated in remodelling and repositioning of reticular ER tubules by hitchhiking on lysosomes. We suspect that altered lysosome morphology in PIKfyve-inhibited cells may impact ER structure and dynamics and ER-lysosome contacts. We performed confocal imaging along with proximity ligation assay experiments and observed significant changes in ER morphology and dynamics in PIKfyve-inhibited cells, as well as possible alterations to contact sites between lysosome and ER. Our work suggests that PIKfyve-induced lysosome coalescence disturbs ER morphology and dynamics.
The Liposome Reconstitution of SARS-CoV-2 Envelope Proteins in Pursuit of a Virus-Like Particle
Authors: Kovacs Norbert
Published: September 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious virus that targets the human respiratory system and continues to be a major challenge facing the world. This research looks to develop a SARS-CoV-2 virus-like particle (VLP) composed of envelope proteins inserted into a liposome to mimic the virus and serve as a platform for further research into the currently understudied envelope protein. A detergent-mediated reconstitution strategy was employed to develop the VLP in which the proteins were reconstituted into liposomes with a lipid composition designed to resemble the viral particle. Through the use of two-photon excitation fluorescence cross-correlation spectroscopy (TPE-FCCS) it will be shown that VLPs can be created with 15-30 proteins per particle, mirroring that of the virus. This work serves as both a first step in creating a more comprehensive VLP incorporating multiple SARS-CoV-2 proteins, as well as a potential platform to study the protein's properties.
الدافعية الذاتية الاكاديمية والتكامل النفسي وعلاقتهما بأداء بعض المهارات كرة القدم للصالات لدى
Authors: Prof. Dr. Yassin Alwan Ismail Al-Tamimi
Published: September 2024

لابد من دراسة سلوك الطلبة في أثناء سعيهم في تحقيق طموحاتهم عند ممارستهم لاختصاصاتهم الرياضية متمثلة بمصادرها الأساسية ضمن إحدى مكونات الشخصية في الدافعية الذاتية والتكامل النفسي وما يرافق ذلك من أفعال مصاحبة عند ممارسة الألعاب الرياضية وكرة القدم للطلاب تعد واحداً من الألعاب الرياضية التي تدرس ضمن مناهج كليات التربية الرياضية التي تتمتع بمهارات وحركات عديدة ونظراً لما تتطلبه هذه اللعبة من مستوى عالٍ بأداء المهارات وزيادة استثمار الجهد المبذول ووقت التعلم الفعلي الأكاديمي الذي تكون فيه الطالبة منشغلة بمحتوى الدرس بمستوى ملائم لقدرتها لتحقيق مستوى أداء بعض المهارات مع محاولة لتصحيح الأخطاء التي ترافق عملية التعلم. لذا هدف البحث الى: -

اعداد مقياس الدافعية الذاتية الأكاديمية وبناء مقياس التكامل النفسي لدى طالبات كليات التربية البدنية وعلوم الرياضة – جامعات الفرات الأوسط
التعرف على العلاقة الارتباطية ما بين الدافعية الذاتية الاكاديمية والتكامل النفسي بأداء بعض مهارات كرة القدم للصالات لدى الطالبات

 استخدم الباحث المنهج الوصفي بالأسلوب المسحي والعلاقات الارتباطية لملاءمته وطبيعة الدراسة أذ شملت عينة البحث على طالبات المرحلة الأولى والثالثة والرابعة في كليات التربية البدنية وعلوم الرياضة جامعات (بابل، كربلاء، الكوفة، القادسية، المثنى) والبالغ عددهن (109) طالب كما استعان الباحث بالإجراءات الخاصة في اعداد وبناء مقياسي (الدافعية الذاتية وبناء كمقياس التكامل النفسي)، واظهرت النتائج البحثية :

ظهرت النتائج وجود علاقة ارتباط معنوية الدالة بين الدافعية الذاتية الاكاديمية والتكامل المقاييس.
Apropiación creativa de tecnología en contextos de encierro: inclusión educativa y social
Authors: San Martín Patricia Silvana , Rodríguez Guillermo Luján , Pidello María Amelia , Cenacchi Marisa , Manero Lucia , Jusama Belén , Bauman Peter , Álvarez Emilia , Diaz Javiera
Published: September 2024

El presente trabajo revela la importancia de la adopción de perspectivas situadas para la apropiación creativa de tecnología orientadas a la inclusión social, especialmenteen contextos de encierro punitivo. Este estudio se propone aportar a la construcción del modelo «Apropiación Creativa Tecnologías-Articulación Contenidos Curriculares» entendiéndolo como una herramienta teóricametodológica. La elaboración de esta se realizó a partir de una prueba piloto en un centro penal juvenil de una provincia Argentina, lo cual posibilitó una aproximación empírica y situada. Este estudio de caso aporta información relevante para los espacios de encierro punitivo donde requieren de un proceso de coconstrucción entre las prácticas educativas formales y no formales. Los resultados posibilitan la comprensión de las necesidades y desafíos en la integración de tecnología en la educación de jóvenes privados de libertad y destacan la necesidad de construir iniciativas innovadoras que comprendan la inscripción de estas orientaciones en los proyectos institucionales.
Cami Mûsikîsinde Erzurum Yöresine Özgü Bir İcra: İşfe‘ Lenâ Duası
Authors: Özfidan Mustafa , Gerçek İsmail Hakkı
Published: September 2024

Cami ve tekkelerde yürütülen ibadet ve zikirler esnasında Kur’ân tilaveti, ezan, tekbir ve ilâhi gibi toplamda otuz altı adet form Türk Din Mûsikîsi literatürüne girmiştir. Cami ve tekke kültürünün zenginliğini gösteren bu örneklerin yanı sıra belirli bölgelerde varlığını sürdüren ve yöresel olarak değerlendirilebilecek icralara da rastlanmaktadır. Bunlardan biri de Erzurum ilinde gelenek olarak yaşayan ve teravih ile vitir namazları arasında okunan “İşfe‘ Lenâ” duasıdır. Çalışmada Erzurum şehri dışında icra edilmeyen ve artık unutulma riskiyle karşı karşıya kalan duanın tespit edilmesi amaçlanmıştır. Bu tespit; “İşfe‘ Lenâ” duasının ismi, tarihi, muhtevası, yaygın etkisi, icracıları, bestesi, tavır ve üslubu gibi özelliklerini ortaya koymanın yanı sıra; duanın notasyon ve makamsal analizini içermektedir. Söz konusu dua bu şehrin kadim geleneklerinden birisi olup etnolojik unsurları bünyesinde barındırması ve şehre ait kültürel bir kimlik oluşturması itibarıyla önem taşımaktadır. Çalışmada etnografik araştırma yöntemi kullanılmış olup doküman analizi, gözlem ve görüşme metotları ile çalışılmış; müzikal ve kültürel analizler yapılmıştır.
Idiopathic Pulmonary Fibrosis: Review of Current Knowledge
Authors: Muri J , Durcová B , Slivka R , Vrbenská A , Makovická M , Makovický P , Škarda J , Delongová P , Kamarád V , Vecanová J
Published: September 2024

Idiopathic pulmonary fibrosis (IPF) is a severe and currently incurable disease that is associated with irreversible fibrotic remodeling of the lung parenchyma. Pathological remodeling of the lung leads to damage of the alveolo-capillary barrier. There is a reduction in the diffusing capacity of the lungs for respiratory gases. Later, changes in the mechanical properties of lung tissue occur - their compliance decreases and respiratory work increases. Impaired respiratory gases exchange with restrictive ventilatory failure lead to tissue hypoxia and muscle weakness. Progressive respiratory insufficiency develops. The triggers of fibrotic remodeling of the lung are currently unknown, as are the pathomechanisms that keep this process active. IPF can only be slowed pharmacologically, not reversed. It is therefore very important to start its treatment as soon as possible. Early detection of IPF patients requires a multidisciplinary approach. Diagnosis, treatment initiation, and monitoring in specialized centers offer the best chance of slowing disease progression, enhancing quality of life, and extending patient survival. In addition to antifibrotic therapy, good lifestyle management, maintenance of physical fitness and treatment of associated chronic diseases such as diabetes and cardiac comorbidities are important. Lung transplantation is an option for some patients with IPF. This is a challenging treatment modality, requiring close collaboration with transplant centers and expert selection of suitable candidates, influenced, among other things, by the availability of suitable donor lungs. Our article aims to provide current information about IPF, focusing on its functional consequences and clinical manifestation. We discuss the molecular and cellular mechanisms potentially involved in IPF development, as well as the morphological changes observed in lung biopsies and high-resolution computed tomography (HRCT) images. Finally, we summarize the existing treatment options.
RESILIENSI EKONOMI PESANTREN MELALUI HOLDING BISNIS HEBITREN: APLIKASI ASSET BASED COMMUNITY DEVELOPMENT
Authors: Ali Jeihan Azhar , Tri Pambekti Galuh , Baroroh Hilmy , Hassany Egha Ezhar Junaeka Putra , Insani Saibil Defi
Published: September 2024

Pesantren is a religious institution that is one of the drivers in the fields of populist economy, MSMEs, and sharia economy, which has potential, especially in the midst of the COVID-19 pandemic. The economic resilience of pesantren is very crucial in the ongoing ecosystem of the pesantren economy. The development of pesantren in responding to the economy has motivated Bank Indonesia to form the Pesantren Economics and Business Association (HEBITREN), especially the Yogyakarta regional office in 2021. The formation of HEBITREN requires contributions from other institutions, especially educational institutions in transforming business model ideas and ideas for business holding between pesantren. The benefits of this service for pesantren administrators are the receipt of input or transfer of knowledge related to the preparation of the Hebitren business model, business planning and RAPB, preparation of standard operating procedures, financial reports, organizational structure and job descriptions, mapping prospective Hebitren managers, and the core business to be run. The study center for the empowerment and economic development of pesantren, UIN Sunan Kalijaga, was present as a companion to HEBITREN in realizing the economic resilience of pesantren through the HEBITREN business holding by applying Asset Based Community Development. The output of this agenda is in the form of a Hebitren business model, business planning and RAPB, preparation of standard operating procedures, financial reports, organizational structure and job descriptions, mapping of prospective Hebitren managers, and the core business to be run.
ANALYSIS OF THE PRODUCT DISTRIBUTION MECHANISM AT THE DISTRIBUTION CENTER OF NURUL JADID ISLAMIC ECONOMIC PERSPECTIVE AFZALUL ROHMAN
Authors: Hidayatulloh Muhammad Andreansyah
Published: September 2024

This This research will analyze the distribution mechanism at the Nurul Jadid Distribution Center from an Islamic Economics perspective according to Afzalur Rahman. The focus includes: (1) The distribution mechanism at the Nurul Jadid Islamic Boarding School, (2) Afzalul Rohman's Islamic Economics view of the distribution mechanism, and (3) Supporting and inhibiting factors in distribution at the center. The results of this research show that the center distribution mechanism namely: making customer levels,: retail stores, agents, distributors, creating their own products (Nurja mineral water, salt, atlas covers and BHS, providing education to customers on how to market in accordance with sharia principles, providing product information according to conditions. In discussing the application of the principles-Islamic economic principles by the Distribution Center (DC) based on the teachings of Afzalul Rahman. DC adopts the principle of Tauhid to realize the welfare of the country, the principle of Maslahah by prioritizing the common interests of Islamic boarding schools and society, and the principle of justice by providing equal services to all consumers. DC applies leadership principles by selecting leaders who understand Islamic principles. Implementation of these principles strengthens the integrity of the distribution system and supports social welfare. This factor assesses the factors supporting distribution efficiency in Distribution Centers (DC), namely effective leadership, adequate infrastructure, and good coordination. No inhibiting factors were found in the DC distribution system.
Stress and Metabolism: The Role of Individual Micronutrients in Correcting Disorders
Authors: Nikitina E. A. , Orlova S. V. , Batysheva T. T. , Balashova N. V. , Alekseeva M. V. , Prokopenko E. V. , Vodolazkaya A. N.
Published: September 2024

In the last decade, there has been a rapid increase in the incidence of both stress-induced mental disorders and metabolic diseases (obesity, diabetes, etc.). These disorders may be based on common pathogenetic mechanisms, including activation of the hypothalamic-pituitary-adrenal axis, changes in cellular homeostasis and energy metabolism. Nutrition can have both positive and negative effects on the body’s adaptive reserves and metabolism. Our article is devoted to the description of the role of micronutrients rarely used to optimize the diet, such as tyrosine, magnesium, trivalent chromium and vitamin-like substances in the regulation of metabolism and stress resistance.
The use of sweeteners and sugar substitutes in the food industry. Sweet proteins as a new alternative
Authors: Maev I. V. , Zaborovsky A. V. , Tsaregorodtsev S. V. , Yunina D. V. , Kolosov Yu. A. , Starovoytova M. Yu. , Tararina L. A.
Published: September 2024

This review examines the consequences of excessive consumption of sweet products on human health and explores the potential of sugar substitutes and intensive sweeteners, including sweet proteins, as their healthier alternatives. Analyzing statistical data on the prevalence of diabetes and obesity, the study highlights the health risks associated with high sugar intake. An extensive review of the properties of various sugar substitutes and sweeteners has been conducted, focusing on their glycemic index and sweetness level. Special attention is given to sweet proteins, such as monellin and brazzein, their structure, and biological effects. Sweet proteins have a significantly high sweetness index and can serve as an alternative to traditional sugar in food production. However, their application in the food or pharmaceutical industry is limited. The study emphasizes the potential of sugar substitutes and sweeteners, especially sweet proteins, in developing food products by reducing sugar content. Nonetheless, further research is required to ensure the safety of sweet proteins and understand their long-term effects on human health.
The effect of physical activity on the brain natriuretic peptide in various conditions of the cardiovascular system: a review of the subject field
Authors: Meshtel A. V. , Miroshnikov A. B. , Smolensky A. V.
Published: September 2024

In this review of the subject field, the brain natriuretic peptide and its predecessor, the N-terminal pro-brain natriuretic peptide, are considered as a marker for evaluating the effectiveness of rehabilitation programs, including physical activity, in diseases such as arterial hypertension, chronic heart failure, coronary heart disease and other diseases. In addition, the reaction of this peptide to physical activity in healthy people is considered.
The role of natural antioxidants and enzyme inhibitors in the prevention of skin aging
Authors: Orlova S. V. , Prokopenko E. V. , Nikitina E. A. , Batysheva T. T. , Balashova N. V. , Alekseeva M. V. , Vodolazkaya A. N.
Published: September 2024

Aging is a progressive degenerative condition accompanied by an increasing loss of physiological integrity and function. Aging is an inevitable process that includes, among other things, an imbalance between antioxidant defenses and reactive oxygen species, changes in protein and mitochondrial turnover, telomere attrition, cellular senescence, epigenetic changes and stem cell depletion. These conditions are associated with mild to moderate inflammation, which always accompanies the aging process and age-related diseases. Skin aging is a very complex biological phenomenon controlled by many internal and external factors. Natural substances are preferred to improve the health and appearance of the skin.
LA INTELIGENCIA ARTIFICIAL GUIANDO AL PUEBLO
Authors: Pereira Uzal José Manuel , García-Morales Lino
Published: September 2024

El desarrollo de la inteligencia artificial y la invasión en todos los ámbitos de la vida pública (incluido el arte) ha abierto un debate que anuncia, una vez más, la muerte del arte. Lo artificial se debate contra lo natural por legitimar su existencia a través de la verdad y la mentira. Para algunos la creatividad está en riesgo en pro de la banalización, para otros se trata de meras imitaciones o copias que vulneran los derechos de propiedad intelectual. El objetivo fundamental de este artículo es poner las ideas en contexto mediante las respuestas a las siguientes preguntas: ¿qué es y qué no es la inteligencia artificial?, ¿qué es y qué no es el plagio?, ¿qué es y qué no es útil de todo este conflicto?, ¿estamos, de verdad, ante un nuevo fin del arte?
METÁFORAS DE LA CIUDAD HIPERMEDIADA EN EL ARTE CONTEMPORÁNEO
Authors: García García Alejandro
Published: September 2024

La visualización de la dimensión informacional vinculada al entorno urbano organiza una percepción articulada mediante un ecosistema de pantallas desde donde emerge la ciudad hipermediada. Este artículo examina el impacto de diferentes producciones artísticas que, como metáforas de la realidad físico-digital, configuran la fenomenología del paisaje dispuesto por el imperativo tecnológico.
Cochambrança Neomedieval: anti-colonialismo e conservadorismo em Ariano Suassuna
Authors: Santiago Berriel Marcelo
Published: September 2024

Este artigo objetiva apresentar argumentos em favor do conceito de neomedievalismo e sua aplicabilidade em um texto de Ariano Suassuna. Primeiramente, exponho parte das discussões em torno da escolha entre os conceitos de medievalismo e neomedievalismo, defendendo tanto a historicidade do último quanto a perspectiva decolonial no campo específico do neomedievalismo latino-americano. Em seguida, demonstro a aplicação prática das reflexões anteriormente mencionadas em uma análise do texto As Cochambranças de Quaderna, peça de 1987 de autoria do escritor paraibano Ariano Suassuna.
Development of property taxation in some post-socialist countries of Central and Eastern Europe
Authors:   SESE “The Academy of Financial Management”, Sokolovska Alla
Published: September 2024

Introduction. According to the National Revenue Strategy until 2030, the development of property taxation in Ukraine should be carried out by switching from property taxation based on the area of real estate to taxation based on its market value in order to increase local budget revenues and improve taxation fairness. Problem Statement. The introduction of taxation of real estate in Ukraine based on its value, which is a difficult task involving painstaking preparatory work and significant financial resources, requires an analysis of the experience of implementing similar transformations in other countries. At the same time, the development of property taxation in the post-socialist countries of Central and Eastern Europe (hereinafter CEE), some of which still tax real estate by area, while others immediately introduced a tax by value, is of greatest interest. The purpose of the article is to determine, based on the analysis of property taxation experience in selected CEE countries, the prerequisites and ways of transition from a tax based on area to a tax based on value. The methods of systemic, structural-functional, comparative analysis, analogies and theoretical generalization are used. Results. The article analyzes the development of property taxation in two CEE countries (Poland and Slovakia), where, like in Ukraine, the basis for recurrent taxes on real estate is its area, and three Baltic countries where ad valorem real estate taxes have been introduced. The author focuses on the prerequisites and features of their introduction, the design of taxes in individual countries, peculiarities of their administration and prospects for reform. The author draws conclusions about the common and specific reasons for delaying the introduction of ad valorem tax in countries where it is based on real estate area. The author identifies the necessary measures and reveals the problems on the way to introduction of the ad valorem real estate tax related to the creation of a sufficiently complete and reliable database on real estate and its market value and keeping it up to date, gradual introduction of mass assessment of land and property, limited administrative capacity, little experience and insufficient resources of local authorities to entrust them with the function of property tax administration.
High-Fidelity Environment Effect on Early Postpartum Haemorrhage Management
Authors: Coşkun Merve , Aslan Ergül , Ünver Vesile , Karabacak Ükke
Published: September 2024

Objective: In order to compare outcomes of a simulation of early postpartum haemorrhage management through a medium-fidelity mannequin in a high-fidelity environment before clinical practicums with those after clinical practicums in nursing students.
Methods: This quasi-experimental study was performed on second-year nursing students (n=61). After the simulation, the students were asked to perform postpartum haemorrhage control in clinical practicums. Data were collected with the State-Trait Anxiety Inventory, Student Satisfaction and Self-Confidence in Learning Scale, Educational Practices Questionnaire, and Student Self-Evaluation Form.
Results: The mean satisfaction, self-confidence, and Educational Practices Questionnaire scores after the simulation were high. The mean scores for feeling competent in involution, haemorrhage control, fundus massage, perineal care, andestablishing appropriate communication with patients and their relatives were 19.18±5.70 after the simulation and 23.83±5,03 after the clinical practicums.
Conclusion: The medium-fidelity simulation in a high-fidelity environment of early postpartum haemorrhage management enhanced the students’ learning satisfaction and self-confidence. This helped them to feel more competent in the clinical practicums.
The Relationship of Trace Element Levels with Obesity and Cardiovascular Health
Authors: Oguz Doganay , Demirbaş Nur , Kutlu Ruhuşen , Kılınç İbrahim
Published: September 2024

Objective: One of the most important factors affecting cardiovascular health is obesity. Trace elements, which play a role in every stage of metabolism, are also related to our cardiovascular health. The aim of this study was to determine serum trace element levels in individuals and to examine the relationship between trace elements and cardiovascular risk.
Methods: This cross-sectional study was conducted with individuals who applied to the outpatient clinic between 01.03.2022-31.04.2022. Sociodemographic characteristics, BMI, and Framingham risk score values were recorded. Serum iron, zinc, copper and selenium levels were analyzed in the laboratory.
Results: A total of 180 individuals were included in the study. Of the individuals, 33.3% were overweight and 32.8% were obese. The mean Framingham Risk Score (FRS) was 9.31±7.99 (1-37). FRS values of normal weight individuals (7.84±3.05) were lower than the mean FRS values of overweight (8.80±3.39) and obese (13.39 ± 6.24) groups (p
Policy Brief: Politik och omställning för grön energiomställning och klimatneutralitet
Authors: Skogsmo Emma , Björklund Martin , Gamez Daniel Benjamin , La Fleur Lina , Nordensvärd Johan , von Malmborg Fredrik
Published: September 2024

Här sammanfattas vår forskning om påverkansarbete, beslutsfattande och förändring av EU:s politik för grön energiomställning och klimatneutralitet. Fokus ligger på resurs- och energieffektiva byggnader, men även energieffektivisering mer generellt och andra områden inom EU:s lagstiftningspaket Fit for 55. Beslutsfattandet kring energieffektivitet och minskad klimatpåverkan är komplext och påverkas av olika faktorer, inklusive intressenter, intressekonflikter och strategier. Bristande förståelse för politiska dynamiker kan hindra effektiv utformning och genomförande av energipolitik, vilket i sin tur kan försvåra arbetet med att uppnå klimatmål och främja hållbar utveckling. I våra projekt lämnas kunskap om processerna kring beslutsfattande och förändring av EU-politiken. Här presenteras ett kunskapsunderlag att dels påverka framtida EU-direktiv om energieffektivitet och byggnaders energiprestanda, dels främja svensk innovation och förbättra implementering av energieffektiviserande åtgärder i byggd miljö i Sverige såväl som EU och globalt. Resultaten visar att en djupare förståelse för sociala, politiska och institutionella faktorer är avgörande för att effektivt driva hållbar energipolitik. Vi betonar även behovet av ökad transparens för lobbyister för att säkerställa en rättvis och öppen politisk process.
A autoestima da mulher negra frente aos padrões de beleza impostos pela branquitude
Authors: Constante Sandra , Carneiro Pedro
Published: September 2024

Cada vez mais mulheres negras vem assumindo sua beleza natural, com todos seus traços, cor da pele, volume e textura de seus cabelos. O cabelo da mulher negra como símbolo de uma resistência vem ganhando espaço onde o liso era soberano. Atualmente podemos dizer que a beleza negra vem sendo aos poucos reconhecida e legitimada em alguns poucos setores, mas continua a encontrar resistência e opositores. Até pouco tempo atrás, o negro não era considerado belo, mas sim sinônimo de traços grosseiros, pouco refinados, uma raça inferior. A estética apreciada e almejada, portanto, é a do padrão europeu, que se mantém ao longo dos anos sendo alimentada e validada pela supremacia branca - branquitude. O processo de colonização deixou cicatrizes. Cicatrizes que de tão profundas não permitiram às mulheres negras enxergarem em si uma beleza única e singular. As tornou mutiladoras de seus próprios corpos e símbolos, encurraladas pela necessidade de inclusão, aceitação, proteção e respeito. Desta forma, este artigo tem como objetivo incentivar mulheres negras a reconhecer e legitimar a beleza afrodescendente, não validando e não se rendendo aos ataques feitos pela indústria cosmética e mídias para se automutilarem para se enquadrarem em um padrão discriminatório, segregador e profundamente racista.
Bidirectionally validated in silico and in vitro formation of specific depth zone-derived chondrocyte spheroids and clusters
Authors: Takada Eiichiro , Mizuno Hayato L. , Takeoka Yoshiki , Mizuno Shuichi
Published: September 2024

3D multicellular self-organized cluster models, e.g., organoids are promising tools for developing new therapeutic modalities including gene and cell therapies, pharmacological mechanistic and screening assays. Various applications of these models have been used extensively for decades, however, the mechanisms of cluster formation, maintenance, and degradation of these models are not even known over in-vitro-life-time. To explore such advantageous models mimicking native tissues or organs, it is necessary to understand aforementioned mechanisms. Herein, we intend to clarify the mechanisms of the formation of cell clusters. We previously demonstrated that primary chondrocytes isolated from distinct longitudinal depth zones in articular cartilage formed zone-specific spherical multicellular clusters in vitro. To elucidate the mechanisms of such cluster formation, we simulated it using the computational Cellular Potts Model with parameters were translated from gene expression levels and histological characteristics corresponding to interactions between cell and extracellular matrix. This simulation in silico was validated morphologically with cluster formation in vitro and vice versa. Since zone specific chondrocyte cluster models in silico showed similarity with corresponding in vitro model, the in silico has a potential to be used for prediction of the 3D multicellular in vitro models used for development, disease, and therapeutic models.
Tlr7 drives sex- and tissue-dependent effects in Sjögren’s disease
Authors: Punnanitinont Achamaporn , Biswas Sheta , Kasperek Eileen M. , Osinski Jason , Zhu Chengsong , Miecznikowski Jeffrey C. , Romano Rose-Anne , Kramer Jill M.
Published: September 2024

Primary Sjögren’s disease (pSD) is a systemic autoimmune disease that has the strongest female predilection of all autoimmune diseases. The underlying mechanisms that govern this sexual dimorphism, however, remain poorly understood. We hypothesized that pSD females would exhibit more robust disease as compared to males, and that Tlr7 controls distinct disease manifestations in males and females. Using a well-established pSD mouse model, we harvested exocrine glands, and pulmonary and renal tissue from males and females and quantified the inflammation present. We then collected salivary glands, spleens, and cervical lymph nodes and performed flow cytometry to assess immune populations implicated in disease. We also harvested sera to examine total and autoreactive antibodies. Our data revealed that pSD mice displayed sex-biased disease, as pSD females showed decreased dacryoadenitis, but increased nephritis as compared to males. Moreover, females exhibited increased proportions of germinal center B cells and CD4+ activated/memory T cells in the periphery. Additionally, salivary gland immune populations were altered in a sex-dependent manner in pSD. Females with pSD also displayed elevated total and autoreactive IgG as compared to males. Additionally, splenic B cell Tlr7 expression was increased in females. We next generated pSD mice that lacked Tlr7 systemically and found that ablation of Tlr7 was primarily protective in pSD females, while Tlr7-deficient pSD males showed heightened disease. Thus, pSD mice display sex-biased disease and these dichotomous manifestations are governed by Tlr7 activation. This study identifies Tlr7 as a druggable target for pSD, and highlights the importance of studying pSD disease mechanisms in both sexes.
Looking for the ideal medication for heart failure with reduced ejection fraction: a narrative review
Authors: Pascual-Figal Domingo , Bayes-Genis Antoni
Published: September 2024

The main goals of the pharmacological treatment of Heart failure with reduced ejection fraction (HFrEF) are the reduction of mortality and the prevention of hospitalizations. However, other outcomes such as improvements in cardiac remodeling and clinical status, functional capacity and quality of life, should be taken into account. Also, given the significant inter-individual and intra-individual variability of HF, and the fact that patients usually present with comorbidities, an appropriate treatment for HFrEF should exert a clinical benefit in most patient profiles irrespective of their characteristics or the presence of comorbidities, while providing organ protection beyond the cardiovascular system. The aim of this narrative review is to determine which are the proven effects of the guideline-directed treatments for HFrEF on five key clinical outcomes: cardiovascular mortality and hospitalization due to HF, sudden death, reverse cardiac remodeling, renal protection and evidence in hospitalized patients. Publications that fulfilled the pre-established selection criteria were selected and reviewed. Renin-angiotensin system (RAS) inhibitors, namely angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARBs) or angiotensin receptor-neprilysin inhibitors (ARNI), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), sodium-glucose co-transporter 2 inhibitors (SGLT2i) show a benefit in terms of mortality and hospitalization rates. ARNI, BB, and MRA have demonstrated a significant positive effect on the incidence of sudden death. ARB, ARNI, BB and SGLT2i have been associated with clear benefits in reverse cardiac remodeling. Additionally, there is consistent evidence of renal protection from ARB, ARNI, and SGLT2i in renal protection and of benefits for hospitalized patients from ARNI and SGLT2i. In conclusion, the combination of drugs that gather most beneficial effects in HFrEF, beyond cardiovascular mortality and hospitalization, would be ideally pursued.
Case Report: A Chinese child with Barth syndrome caused by a novel TAFAZZIN mutation
Authors: Che Mingxuan , Li Fuhai , Jia Yaning , Liu Qingzheng , Hu Jian , Zhang Jidong , Liu Shiguo
Published: September 2024

Barth syndrome (BTHS) is a rare X-linked recessive genetic disorder characterized by a broad spectrum of clinical features including cardiomyopathy, skeletal myopathy, neutropenia, growth delay, and 3-methylglutaconic aciduria. This disease is caused by loss-of-function mutations in the TAFAZZIN gene located on chromosome Xq28, resulting in cardiolipin deficiency. Most patients are diagnosed in childhood, and the mortality rate is highest in the early years. We report a case of acute, life-threatening metabolic decompensation occurring one day after birth. A novel TAFAZZIN splice site mutation was identified in the patient, marking the first reported case of such a mutation in BTHS identified in China. The report aims to expand our understanding of the spectrum of TAFAZZIN mutations in BTHS.
Reduction of hyperglycemia in STZ-induced diabetic mice by prophylactic treatment with heat-killed Mycobacterium aurum: possible effects on glucose utilization, mitochondrial uncoupling, and oxidative stress in liver and skeletal muscle
Authors: Abdallah Farid , Bazzi Samer , Akle Charles , Bahr Georges M. , Echtay Karim S.
Published: September 2024

Background

In addition to conventional treatment and modifications in physical activity and diet, alternative strategies have been investigated to manage, prevent, or delay diabetes in humans. In this regard, one strategy has relied on the immunomodulatory properties of mycobacteria, whereby Bacillus Calmette–Guerin, an attenuated live strain of Mycobacterium bovis, has been shown to improve glycemic control in patients with diabetes and to alleviate hyperglycemia in selected murine models of diabetes. A novel heat-killed (HK) whole-cell preparation of Mycobacterium aurum (M. aurum) is currently under development as a potential food supplement; nevertheless, its potential bioactivity remains largely unknown. Thus, the present study investigated the potential prophylactic anti-diabetic effects of HK M. aurum in streptozotocin (STZ)–induced diabetic mice.

Methods

Mice were divided into three groups: the STZ-induced diabetic group was injected with a single intraperitoneal high dose of STZ, the HK M. aurum–treated diabetic group was prophylactically treated with three doses of HK M. aurum 6 weeks before STZ injection, and the control non-diabetic group was given three intradermal injections of borate-buffered saline and an intraperitoneal injection of citrate buffer. Liver lactate dehydrogenase (LDH), uncoupling protein 2 (UCP2), and glucose transporter 2 (GLUT2) and skeletal muscle LDH, UCP3, and GLUT4 protein expression levels in different mouse groups were determined by Western blot.

Results

Our results indicated that HK M. aurum did not cause any significant changes in glycemic levels of normal non-diabetic mice. Prophylactic administration of three doses of HK M. aurum to diabetic mice resulted in a significant reduction in their blood glucose levels when compared to those in control diabetic mice. Prophylactic treatment of diabetic mice with HK M. aurum significantly restored their disturbed protein expression levels of liver UCP2 and LDH as well as of skeletal muscle UCP3. On the other hand, prophylactic treatment of diabetic mice with HK M. aurum had no significant effect on their liver GLUT2 and skeletal muscle GLUT4 and LDH protein expression levels.

Conclusions

Our findings provide the first evidence that HK M. aurum possesses a hyperglycemia-lowering capacity and might support its future use as a food supplement for the amelioration of diabetes.
The association of triglyceride-glucose index and combined obesity indicators with chest pain and risk of cardiovascular disease in American population with pre-diabetes or diabetes
Authors: Zheng Dongze , Cai Jiamiao , Xu Sifan , Jiang Shiyan , Li Chenlin , Wang Bin
Published: September 2024

Aim

To investigate the correlation of the triglyceride-glucose (TyG) index and its combined obesity indicators with chest pain and cardiovascular disease (CVD) in the pre-diabetes and diabetes population.

Methods

This cross-sectional investigation encompassed 6488 participants with diabetes and pre-diabetes who participated in the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016. The association of the TyG and combined obesity index with chest pain and CVD was investigated using weighted logistic regression models and restricted cubic spline (RCS) analysis. The receiver operating characteristic (ROC) curve analysis was performed to compare different indicators.

Results

In multivariate logistic regression fully adjusted for confounding variables, our analyses revealed significant associations between TyG, TyG-BMI, TyG-WC, and TyG-WHtR and chest pain, with adjusted ORs (95% CI) of 1.21 (1.05, 1.39), 1.06 (1.01, 1.11), 1.08 (1.04, 1.14), and 1.27 (1.08, 1.48), respectively. For total-CVD, the adjusted ORs (95% CI) were 1.32 (1.08, 1.61), 1.10 (1.03, 1.17), 1.13 (1.06, 1.19), and 1.63 (1.35, 1.97), respectively, among which TyG, TyG-WC, and TyG-WHtR present curvilinear associations in RCS analysis (all P-nonlinear < 0.05). Furthermore, the ROC curve showed that TyG-WC had the most robust predictive efficacy for total-CVD, coronary heart disease (CHD), and myocardial infarction (MI), while TyG-WHtR had the best predictive ability for angina and heart failure.

Conclusion

There are significant associations of TyG and its related indicators with chest pain and total-CVD among the pathoglycemia population. TyG-WC and TyG-WHtR demonstrated superior predictive capability for the incidence of cardiovascular events.
A real-world study of hereditary angioedema patients due to C1 inhibitor deficiency treated with danazol in the Brazilian Public Health System
Authors: Ritter Alessandra Mileni Versuti , Silva Suelen , de Paula Robson , Senra Juliana , Carvalho Fabio , Ribeiro Tatiane , Valle Solange Oliveira Rodrigues
Published: September 2024

Introduction

Hereditary angioedema (HAE) due to C1 inhibitor (C1-INH) deficiency is an ultra-rare autosomal dominant inherited disease that affects 1 in 67,000 people in the world. The attacks are based on subcutaneous and submucosal edema that can lead to death if not properly managed. Considering the lack of information on the clinical management of Brazilian patients with HAE, this study aimed to identify and characterize patients with HAE-C1-INH that used danazol prophylactic treatment in the Brazilian Public Health System (SUS) and the healthcare resource utilization (HCRU).

Methods

This was an observational retrospective database study with patients treated with danazol from January 2011 until December 2021 within the SUS. The HAE cohort included patients with 12 years or older with at least one record for ICD-10 D84.1, one claim for danazol record, and at least 6 months of available history in the database.

Results

Our study included 799 patients treated in the SUS, with a mean (SD) age at danazol initiation of 40 years (16). The number of patients with HAE showed a similar distribution over this 10-year period analyzed with the highest number of patients in 2015 (n = 509) and 2016 (n = 480). A total of 253 (32%) patients had a record of at least one attack. Of those, 45 (17.8%) had at least one procedure HAE-related hospital admission, and 128 (50.6%) had at least one HAE-related hospital admission. The mean (SD) hospitalization length of stay was 5 (8) days. Over 14% (n = 36) of HAE patients with attack (n = 253) had at least one HAE-related ICU admission.

Conclusion

This database study is the strategy used to allow us to find and describe the characteristics of patients with HAE who use danazol for long-term prophylaxis in the SUS and identify HCRU outcomes of interest such as hospitalizations, inpatient, and outpatient settings. The high rate of attacks, hospitalizations, and general resource uses highlights the necessity to increase awareness of new strategies and accurate approaches to treat HAE patients. Therefore, our findings are important indicators that our health system and guidelines need to be revised and improved to properly diagnose, treat, and assist patients with HAE.
Predicting microbe–disease association based on graph autoencoder and inductive matrix completion with multi-similarities fusion
Authors: Shi Kai , Huang Kai , Li Lin , Liu Qiaohui , Zhang Yi , Zheng Huilin
Published: September 2024

Background

Clinical studies have demonstrated that microbes play a crucial role in human health and disease. The identification of microbe-disease interactions can provide insights into the pathogenesis and promote the diagnosis, treatment, and prevention of disease. Although a large number of computational methods are designed to screen novel microbe-disease associations, the accurate and efficient methods are still lacking due to data inconsistence, underutilization of prior information, and model performance.

Methods

In this study, we proposed an improved deep learning-based framework, named GIMMDA, to identify latent microbe-disease associations, which is based on graph autoencoder and inductive matrix completion. By co-training the information from microbe and disease space, the new representations of microbes and diseases are used to reconstruct microbe-disease association in the end-to-end framework. In particular, a similarity fusion strategy is conducted to improve prediction performance.

Results

The experimental results show that the performance of GIMMDA is competitive with that of existing state-of-the-art methods on 3 datasets (i.e., HMDAD, Disbiome, and multiMDA). In particular, it performs best with the area under the receiver operating characteristic curve (AUC) of 0.9735, 0.9156, 0.9396 on abovementioned 3 datasets, respectively. And the result also confirms that different similarity fusions can improve the prediction performance. Furthermore, case studies on two diseases, i.e., asthma and obesity, validate the effectiveness and reliability of our proposed model.

Conclusion

The proposed GIMMDA model show a strong capability in predicting microbe-disease associations. We expect that GPUDMDA will help identify potential microbe-related diseases in the future.
Impact of climate warming on soil microbial communities during the restoration of the inner Mongolian desert steppe
Authors: Qiao Jirong , Zheng Jiahua , Li Shaoyu , Zhang Feng , Zhang Bin , Zhao Mengli
Published: September 2024

Introduction

Grazer exclosure is widely regarded as an effective measure for restoring degraded grasslands, having positive effects on soil microbial diversity. The Intergovernmental Panel on Climate Change (IPCC) predicts that global surface temperatures will increase by 1.5–4.5°C by the end of the 21st century, which may affect restoration practices for degraded grasslands. This inevitability highlights the urgent need to study the effect of temperature on grassland soil microbial communities, given their critical ecological functions.

Methods

Here, we assessed the effects of heavy grazing (control), grazer exclosure, and grazer exclosure plus warming by 1.5°C on soil microbial community diversity and network properties as well as their relationships to soil physicochemical properties.

Results and discussion

Our results showed that grazer closure increased soil microbial richness relative to heavy grazing controls. Specifically, bacterial richness increased by 7.9%, fungal richness increased by 20.2%, and the number of fungal network nodes and edges increased without altering network complexity and stability. By contrast, grazer exclosure plus warming decreased bacterial richness by 9.2% and network complexity by 12.4% compared to heavy grazing controls, while increasing fungal network complexity by 25.8%. Grazer exclosure without warming increased soil ammonium nitrogen content, while warming increased soil nitrate nitrogen content. Soil pH and organic carbon were not affected by either exclosure strategy, but nitrate nitrogen was the dominant soil factor explaining changes in bacterial communities.

Conclusion

Our findings show that grazer exclosure increases soil microbial diversity which are effective soil restoration measures for degraded desert steppe, but this effect is weakened under warming conditions. Thus, global climate change should be considered when formulating restoration measures for degraded grasslands.
Outdoor nighttime light exposure (light pollution) is associated with Alzheimer’s disease
Authors: Voigt Robin M. , Ouyang Bichun , Keshavarzian Ali
Published: September 2024

Introduction

Alzheimer’s disease (AD) prevalence has increased in the last century which can be attributed to increased lifespan, but environment is also important. Exposure to artificial light at night is one environmental factor that may influence AD.

Methods

This study evaluated the relationship between outdoor nighttime light exposure and AD prevalence in the United States using satellite acquired outdoor nighttime light intensity and Medicare data.

Results

Higher outdoor nighttime light was associated with higher prevalence of AD. While atrial fibrillation, diabetes, hyperlipidemia, hypertension, and stroke were associated more strongly with AD prevalence than nighttime light intensity, nighttime light was more strongly associated with AD prevalence than alcohol abuse, chronic kidney disease, depression, heart failure, and obesity. Startlingly, nighttime light exposure more strongly associated with AD prevalence in those under the age of 65 than any other disease factor examined.

Discussion

These data suggest light exposure at night may influence AD, but additional studies are needed.
[68Ga]Ga-FAPI PET/CT in brain tumors: comparison with [18F]F-FDG PET/CT
Authors: Liu Ya , Ding Haoyuan , Cao Jianpeng , Liu Guangfu , Chen Yue , Huang Zhanwen
Published: September 2024

Purpose

To investigate the feasibility of [68Ga]Ga-FAPI PET/CT in brain tumor imaging and to compare it with [18F]F-FDG PET/CT.

Methods

25 patients with MRI-suspected brain tumors were included in the study. They underwent whole body [18F]F-FDG PET/CT and [68Ga]Ga-FAPI PET/CT and brain scans. The target-to-background ratio (TBR) of brain tumors was calculated with the background of surrounding normal brain tissues uptake. The SUVmax and TBR of [18F]F-FDG PET/CT and [68Ga]Ga-FAPI PET/CT were compared. Additionally, the correlation between the uptake of the tracer by lesions with the greatest diameter of the lesion, the breadth of the oedema band, and the enhancement scores of the MRI enhancement scans was analyzed.

Result

[68Ga]Ga-FAPI PET/CT was superior to [18F]F-FDG PET/CT for lesion detection, especially for brain metastases. Among gliomas, only high-grade gliomas uptake [68Ga]Ga-FAPI. Compared with [18F]F-FDG PET/CT, [68Ga]Ga-FAPI PET/CT had a lower SUVmax but a significantly better TBR. On [68Ga]Ga-FAPI PET/CT, the TBR may be associated with brain tumor blood-brain barrier disruption.

Conclusions

[68Ga]Ga-FAPI PET/CT is a promising imaging tool for the assessment of brain tumors. Lack of physiological uptake of [68Ga]Ga-FAPI in normal brain parenchyma results in high TBR values, leading to better visualization of lesions and contributing to subsequent targeted therapy studies.

Advances in knowledge

Clinical utility of [68Ga]Ga-FAPI PET/CT in brain tumors remains unclear, and there aren’t many similar studies in the literature. We evaluated the role of [68Ga]Ga-FAPI PET/CT in diagnosing brain tumors.