bluuebunny/crossref_metadata_2025 huggingface dataset:
MANHAJ KRITIKAN MUḤADDITHŪN TERHADAP RIWAYAT SIRAH DAN PENERAPANNYA DALAM PENULISAN SIRAH
Authors: Fadzlan Abd Kadir  , Roshimah Shamsudin
Published: June 2022

Efforts in preserving the hadiths of Prophet Muhammad (PBUH) obligate the hadith scholars to filter narrations attributed to the Prophet (PBUH), including those on his biography. These efforts have given birth to a methodology used to criticise the narrations since the days of the companions. However, applying the methodology to narrations pertaining to the biography of the Prophet (PBUH) or the sīrah has been a challenging task given the multitude of narrations that do not meet the criteria of acceptance by the muḥaddithun that infiltrate the knowledge of sīrah. Thus, this paper aims to scrutinise the methods of criticising hadiths employed by hadith scholars and the application of these methods on the works on sīrah. A qualitative study was conducted by collecting data from the major works on hadiths and sīrah. The finding demonstrates that the muḥaddithun’s critiques of the sīrah narrations are based on the critiques on sanad and matan. In applying the method, it is imperative to be murunah. This is done by placing each narration at its correct position by prioritising authentic and ḥasan hadiths, in addition to being tasahul on the permissible aspects based on the prescribed discipline.
Оптимізація режиму стерилізації експлантів Juglans regia L.
Authors: Ryzhenko T. S.
Published: June 2022

Презентовано результати дослідів зі стерилізації експлантів горіха волоського (Juglans regia L.) із використанням різних хімічних речовин. Дослідження проведено в лабораторії мікроклонального розмноження УкрНДІЛГА. Відібрано зразки з дерева, яке росте у місті Харкові, з січня до квітня включно. Як первинні експланти використовували фрагменти здерев’янілих пагонів завдовжки 1–2 см. Дослідження охоплювали виявлення кращих режимів стерилізації рослинного матеріалу горіха волоського для подолання фенольного окислення та запобігання ураженню грибами та іншими патогенами. Як основні стерилізаційні речовини використано Лізоформін-3000, нітрат срібла (AgNO3), антибіотик Цефотаксим. Життєздатність експлантів оцінювали через 25 діб. Результати проведених досліджень свідчать, що використання Лізоформіну-3000 як стерилізувального агента не є ефективним. Застосування нітрату срібла AgNO3 не сприяло подоланню внутрішньої інфекції, що призвела до подальшої некротизації мікропагонів горіха. Використання антибіотика Цефотаксим в поживному середовищі (MS без модифікацій) дало змогу подолати фенольну інтоксикацію та розвиток інфекції в експлантах горіха волоського.
In Silico Study of the Cardioactive Constituents of Tinospora crispa
Authors: Haque Ehfazul , Anjum Juhaer , Bahar Nasiba Binte , Chowdhury Jakir Ahmed , Chowdhury Abu Asad , Kabir Shaila , Sikder Md Al Amin , Amran Md Shah
Published: June 2022

Tinosporacrispais a well-known medicinal plant utilized for hypertension. A number of studies have irrefutably established this characteristic, and there have been attempts to narrow down the possible plant constituents responsible. One of the most efficient ways of carrying out this search is the employment of in silico methods, which constitute molecular docking and interaction studies with particular endogenous macromolecular targets (assumed as receptors) using the plant compounds. Drug compound optimization can also be assisted by in silico pharmacokinetic and chemical analyses. In this study, protein and drug databases are used as the source of target and ligand libraries, respectively. AutodockVina and Discovery Studio are used for docking and interaction studies. Afterward, 6 cardioactive compounds are identified, and their potential mechanisms of action are elucidated. Later on, SwissADME and ProTox-II servers are used to assess the chemical and pharmacokinetic properties.
Dhaka Univ. J. Pharm. Sci. 20(3): 293-306, 2022 (June) Centennial Special Issue
Drug Manufacturing and Access to Medicine in Nepal – A Literature Review of Challenges and Proposed Remediation
Authors: Bhatt Hemant , Santosh KC , Thapa Panna
Published: June 2022

In recent years considerable attention has been paid to the issue of access to medicine. Access to medicine cannot depend on the decision of private industries only but also on government policies and strategies. According to National Health Policy2019, it is the right of all citizens to have basic health care service including access to safe, efficacious and quality medicine. Nepal is a landlocked country in South Asia. Nepal is a diverse country with a varied culture, language, and biodiversity, but generally affected by the common disease (e.g. tuberculosis, COPD, diarrhoeal disease, diabetes and malaria). There are 65 plus private pharmaceutical industries in operation in Nepal and approximately 60% of drugs are imported from India and third-world countries. The only government owned pharmaceutical industry is ‘Nepal Aushadhi Limited’ which is not fully operational in manufacturing essential medicine. Private manufacturers focus mainly on brand competition for private consumption but not in essential medicines. Some essential medicines are totally imported from India and other countries (e.g. insulin). The Nepal government has Free Drug List (FDL) consisting 70 medicines that should be provided free to the all patients but these are not accessible to all citizen of rural areas due to poor logistic management, supply chain and transportation facilities. Quality and adequacy of health services and medicines are the main problem in rural areas. This article mainly focuses on challenges of drug manufacturing and access to safe, efficacious and quality medicines in Nepal. It also emphasizes on strategies and policies being implemented to solve these problems. It is obvious that solving the challenges to provide safe, efficacious and quality medicine is collective responsibility of government of Nepal, private manufacturing industries, regulatory bodies, health professional, the patient and NGO, INGOs working on healthcare system of Nepal.
Dhaka Univ. J. Pharm. Sci. 20(3): 373-379, 2022 (June) Centennial Special Issue
El cambio de fase como estrategia pasiva: Evaluación del rendimiento térmico-energético en edificaciones en Panamá
Authors: Berrocal Diana , Aranda Rubí , Santamaría Steyci , Vigil Aníbal , Chen Miguel Agustin
Published: June 2022

Grandes esfuerzos han sido enfocados en hallar formas que permitan reducir el consumo energético, ya que actualmente la producción de energía es uno de los grandes contaminantes atmosféricos. Así, una estrategia que parece ser efectiva es la implementación de Materiales de Cambio de Fase (Phase Change Materials, PCM), que debido a su alta cantidad de energía tiene la capacidad de almacenar una cantidad significativa de energía. De aquí surge el objetivo de evaluar diferentes materiales de cambio de fase para determinar su influencia en la mejorar el confort interno de los edificios, y que no impacten negativamente al ambiente. Se lleva a cabo una revisión literaria sobre la aplicación de materiales de cambio de fase como elemento pasivo en la construcción de edificios y las mejoras energéticas que brinda. Se detallan las metodologías utilizadas en las simulaciones y experimentos llevados a cabo en otras investigaciones, así como la descripción de los materiales de cambio de fase estudiados. Se identifican los criterios de evaluación utilizados los cuales permiten analizar el comportamiento energético de los materiales de cambio de fase, y se describe su desempeño energético. Finalmente, se evalúa el desempeño energético de cinco materiales de cambio de fase, bajo el clima de la Ciudad de Panamá, por medio de una simulación realizada en DesignBuilder, basados en los mismos indicadores de desempeño antes establecidos, de donde se obtiene que el material de cambio de fase PCM1 es el que presenta mejor desempeño.
Application of mobile-assisted blended learning to College English teaching
Authors:   Beijing Institute of Petrochemical Technology, No. 19, Qingyuanbei Rd, Huangcun, Daxing District, Beijing, China., Ge Shan
Published: June 2022

The development of information and communication technology in education requires interactive and individualized teaching and deep learning. The current classroom teaching of College English fails to meet the new requirements of the digital era, which leads to a low level of learner engagement and unsatisfying learning outcomes. To meet the needs of millennial students, a mobile-assisted blended course model is designed for College English teaching following the basic tenets of Constructivism and Activity Theory. The model incorporates the strengths of self-directed online learning and face-to-face offline instruction to maximize results by strengthening the role of the teacher as facilitator and defining a clear division of labor between students and the teacher at the pre-class, in-class and post-class learning stages. An experiment with the blended model was carried out in one of the author’s College English classes of 28 students for a whole semester and the experimental data were collected through tests and questionnaires. A comparison between the pre-test and post-test scores reveals that students’ English language proficiency improves after mobile-assisted blended learning was used for teaching. The survey conducted at the end of the experiment shows that mobile-assisted blended learning helps to motivate students’ interest in English learning, increase the degree of learner engagement, and improve learning outcomes. The findings suggest that to produce optimal learning outcomes, the instructor must seek to empower every student to become an active participant in the learning process by breaking traditional boundaries of classroom instruction and embracing new advances in learning technologies. Keywords: Blended learning, mobile-assisted, college english, blended course model, learner engagement, learning outcomes.
PENGARUH MOTIVASI BELAJAR TERHADAP HASIL BELAJAR MATEMATIKA SISWA DI SMPN 2 TIRTAMULYA
Authors: Nugroho Risky , Attin Warmi
Published: June 2022

Purpose of this study was to determine the effect of learning motivation to student mathematics learning outcomes at SMPN 2 Tirtamulya. The method used is a quantitative method. The population in this study were all students of SMP Negeri 2 Tirtamulya for the academic year 2021/2022, with 18 students of class VIII being the research sample. Data learning motivation and mathematics learning outcomes were obtained using questionnaires and documentation. The independent variable in this study is learning motivation, while the dependent variable is the result of learning mathematics. The data obtained were then analyzed using descriptive statistics and inferential statistics. The results showed that learning motivation had a significant positive effect to student mathematics learning outcomes at SMP Negeri 2 Tirtamulya. The level of closeness of the relationship between learning motivation and student mathematics learning outcomes is in the very strong category. The magnitude of the influence of learning motivation on students' mathematics learning outcomes is 95.84%. Meanwhile, the influence of other factors on the mathematics learning outcomes of SMP Negeri 2 Tirtamulya students is 4.16%.
The computer modelling of human TRH receptor, TRH and TRH-like peptides.
Authors: Bílek R , Stárka L
Published: June 2022

The aim of this work was to verify the possibility of interactions between the human TRH receptor (an integral membrane protein which belongs to family 1 of G-protein coupled receptors) and TRH-like peptides presented in the prostate gland. These peptides are characterized by substitution of basic amino acid histidine (related to authentic TRH) for neutral or acidic amino acid, such as glutamic acid, phenylalanine, glutamine or tyrosine. The physiological function of TRH-like peptides in peripheral tissues is not precisely known. However, according to our recent experiments, we assume the existence of a local hormonal network formed by TRH-like peptides and TSH in the prostate gland. The network can be associated with circulating thyroid and steroid hormones, and may represent a new regulatory mechanism influencing the proliferative ability of prostatic tissue. A similar network of authentic TRH and TSH was already found in the gastrointestinal tract. The experimentally determined 3D-structures of human TRH receptor (hTRHr) and TRH-like peptides are not available. From this point of view we used de novo modeling procedures of G-protein coupled receptors on an automated protein modeling server used at the Glaxo Wellcome Experimental Research (Geneva, Switzerland). 3D-structures of TRH-like peptides were determined with a computer program CORINA (written by the team of J. Gasteiger, Computer-Chemie-Centrum and Institute for Organic Chemistry, University of Erlangen-Nurenberg, Germany). The generated PDB files with 3D-coordinates were visualized with Swiss-Pdb Viewer Release 3.51 (Glaxo Wellcome). From recent results it is evident that polar amino acids belonging to the extracellular terminus of hTRHr transmembrane regions can participate in interactions between TRH and hTRHr. There is no direct evidence that TRH-like peptides interact with the presented hTRHr model. On the contrary, with respect to the similar 3D-shape and the identity of terminal amino acids, it appears that these interactions are highly probable as well as the nearly 100 % cross-reactions between TRH or TRH-like peptides and antibody specific against authentic TRH. Closed terminal amino acids (pyroglutamic acid and proline-amide) of TRH or TRH-like peptides are important for these interactions. Desamido-TRH or glutamyl metabolites will be repelled by the negative potential of ASP195 (E: D93) and GLU298 (G: E137).
Consciousness and life after death in the evolution of intelligence
Authors: Senarath Dayathilake Kande Lekamalaya
Published: June 2022

No scientific study has been able to find evidence of an afterlife, and consciousness is still one of the most challenging questions. Here, I show a hypothesis for consciousness and the probability of an afterlife through three simple thought experiments and theoretical evidence, yet I do precisely understand the mechanism. I found that consciousness might be discussed from three fundamental theories: quantum-level particles of neuronal function according to quantum mechanics; the brain, neurons, and molecules behave to general relativity, and a new theory is needed for ultraquantum particles. Simultaneously, a person or animal's death selection of a new neuronal system's quality of contemporary life might depend on the state of the finally evolving ultraquantum genome in the natural evolution of intelligence. Ultraquantum particles might emit and bond simultaneously with the suitable early nervous system or embryo when a brain dies.
PENGARUH PARAMETER PEMOTONGAN PADA PROSES FRAIS TERHADAP KEKASARAN PERMUKAAN MATERIAL ALUMINIUM 6061
Authors: Pratama Indra , Rizza Muhammad Akhlis
Published: June 2022

Proses pemesinan yang biasanya digunakan dalam proses produksi membutuhkan ketelitian yang tinggi untuk mendapatkan hasil yang baik. Ketelitian, kepresisian dan kualitas permukaan menjadi prioritas utama yang menjadi acuan dalam pengerjaan proses pemesinan. Hasil permukaan benda kerja yang baik salah satu yang diharapkan dari setiap pengerjaan. Tingkat kepresisian dan kekasaran permukaan benda kerja yang dihasilkan harus sesuai dengan kebutuhan. Menyadari bahwa permukaan yang dikerjakan pada proses pemesinan selalu timbul kekasaran, gelombang dan kerataan pada permukaan.Tujuan penelitian ini adalah untuk mengetahui pengaruh kecepatan putaran spindel dan kedalaman pemakanan terhadap tingkat kekasaran permukaan material aluminium 6061 menggunakan mesin frais CNC dengan tipe VMC 1000B. Metode penelitian ini adalah eksperimen menggunakan mesin frais CNC tipe VMC 1000B dengan material Aluminium 6061. Variasi pemotongan berupa kecepatan putaran spindle (1700 rpm,1800 rpm,1900 rpm) dan kedalaman pemakanan (0,1 mm, 0,2 mm, 0,3 mm). Proses pengefraisan dengan melakukan penyayatan permukaan benda kerja, setelah itu dilakukan uji kekasaran permukaan menggunakan 2 alat, yang pertama menggunakan alat surface roughness tester dan yang kedua menggunakan mikroskop digital guna mengetahui hasil kekasaran permukaan material Aluminium 6061. Hasil penelitian pengaruh variasi kecepatan spindel dan kedalaman pemakanan pada proses frais terhadap kekasaran permukaan material Aluminium 6061 diperoleh, hasil uji statistik dari pengujian eksperimen faktorial menggunakan software Minitab 19 maka yang berpengaruh paling signifikan adalah tingkat kekasaran benda kerja berdasarkan kecepatan putaran spindel. Hal ini dibuktikan nilai P-Value 0.000 dengan α = 0.05. Kecepatan putaran spindel dengan nilai kekasaran permukaan terendah adalah kecepatan putaran spindel yang terbesar, karena menghasilkan kekasaran permukaan alumunium 6061 paling rendah dengan nilai uji kekasaran permukaan 0.17 µm.
Metodologias ativas e formação ética no contexto do novo paradigma tecnológico: experiências de docentes da Universidade Estadual do Paraná – Unespar
Authors: Pataro Ricardo Fernandes , De Araújo Ulisses Ferreira
Published: June 2022

Este artigo apresenta dados de pesquisa de pós-doutorado que estudou o uso de metodologias ativas por docentes da Universidade Estadual do Paraná. Foram utilizados questionários online individuais com perguntas a docentes de cada campus da instituição. Consideramos que as metodologias ativas podem ser conjugadas com as tecnologias e entendidas como oportunidade de inserir, no contexto do Ensino Superior, a preocupação com a formação ética de estudantes. Os resultados mostraram uma maior ocorrência da formação ética nas aulas em que havia uso de metodologias ativas. Além disso, mais da metade dos(as) docentes participantes da pesquisa afirmaram conhecer e utilizar metodologias ativas e quase a totalidade declarou utilizar também tecnologias em classe. Entretanto, ao descreverem uma de suas aulas, 58,3% dos docentes não apresentaram características das metodologias ativas e nem uso de tecnologias. Os dados sugerem que os(as) docentes compreendem a importância e desejam fazer uso de tecnologias e de metodologias ativas, considerando sobretudo a necessidade de formação ética dos futuros profissionais. Por outro lado, as aulas descritas nem sempre concretizam esse desejo. Considerando que o corpo docente da Unespar é jovem e está em formação, os dados nos ajudam a entender que propor o uso de metodologias ativas contemplando uma formação voltada para vivências morais – especialmente no contexto tecnológico que marca a sociedade contemporânea – exige um investimento não somente formação continuada como também em formação inicial, além da necessidade de pensar em um enfrentamento de crenças e concepções pessoais que incidem sobre as práticas pedagógicas desenvolvidas nas salas de aula do Ensino Superior.
SENTIDOS ATRIBUÍDOS POR PROFESSORES-TUTORES AOS SEUS (NÃO)SABERES DIDÁTICO-PEDAGÓGICOS
Authors: Moreira Jefferson da Silva , Nunes Mascarenhas Aline Daiane
Published: June 2022

Este artigo apresenta resultados de pesquisa qualitativa, do tipo estudo de caso, que objetivou compreender quais são os saberes didático-pedagógicos mobilizados por tutores no método Problem-Based Learning (PBL) do curso de Engenharia de   Computação de uma universidade pública baiana. A seguinte questão subsidiou o   processo investigativo: qual repertório de saberes didáticos e pedagógicos são mobilizados por professores-tutores de uma universidade baiana no processo de mediação didática no método PBL? Os dados foram coletados por meio de casos de ensino e questionários aplicados a oito professores-tutores. Os resultados apontam   que os saberes dos participantes é frágil, pois a maioria diz não ter formação sobre esses aspectos, o que reverbera em exercício docente intuitivo no Ensino Superior.
Sustainable Intensification and Climate-Smart Yam Production for Improved Food Security in West Africa: A Review
Authors: Owusu Danquah Eric , Danquah Frank Osei , Frimpong Felix , Dankwa Kwame Obeng , Weebadde Cholani Kumari , Ennin Stella Ama , Asante Mary Otiwaa Osei , Brempong Mavis Badu , Dwamena Harriet Achiaa , Addo-Danso Abigail , Nyamekye Daniel Rexford , Akom Mavis , Opoku Abena Yeboaa
Published: June 2022

Intensification of staple food crops such as Yam (Dioscorea spp.) while sustaining the environment is imperative in providing food for the expected 9.6 billion global population by 2050. In West Africa, amid the threat posed by climate change on food security, yam production is associated with deforestation and land degradation. Integrated soil fertility management and improved staking options for intensification and sustainable yam production on continuously cropped fields hold the key to addressing this challenge. This review evaluates the last decade's yam production trends in West Africa and in three leading yam-producing countries, Nigeria, Ghana, and Côte d'Ivoire, using the Food and Agriculture Organization Corporate Statistical Database (FAOSTAT) data. A production increase of 1.72, 1.43, and 1.35 times resulted in an area harvest increase of 2.25, 1.23, and 1.59 times in Nigeria, Ghana, and Côte d'Ivoire, respectively. Nigeria and Côte d'Ivoire had the worst yam productivity across the decade by producing at an average yield 17.3 and 12.5%, respectively, of the estimated potential yam yield (50 t ha−1). Even in Ghana, where the productivity increased across the decade, the average productivity was 33% of the estimated potential yield. Thus, it can be observed that the primary reason for the increase in yam production across the globe and in West Africa is mainly because of the increase in area under cultivation in the major yam-producing countries. The projected future erratic rainfall and elevated daily mean temperature as a result of climate change would cause declining tuber yields. Meanwhile, the importation of food such as rice as a strategy to improve food availability cannot be accessed by poor rural households due to the strong correlation between international food price hikes and prices of these foods. However, there is less relationship between international yam price hikes and yam prices in West Africa. Therefore, yam production and sustenance could be vital for food security for the increasing population of West Africa. This study reviews current research on soil fertility and staking options for sustaining yam production on continuously cropped fields. Promotion and adoption of these improved technologies would enhance food security and contribute to achieving Sustainable Development Goals 1 (No poverty), 2 (Zero hunger), 13 (Climate action), and 15 (Life on land).
Virtual Reality as Tool for Bioprinting Quality Inspection: A Proof of Principle
Authors: Gretzinger Sarah , Schmieg Barbara , Guthausen Gisela , Hubbuch Jürgen
Published: June 2022

As virtual reality (VR) has drastically evolved over the past few years, the field of applications of VR flourished way beyond the gaming industry. While commercial VR solutions might be available, there is a need to develop a workflow for specific applications. Bioprinting represents such an example. Here, complex 3D data is generated and needs to be visualized in the context of quality control. We demonstrate that the transfer to a commercially available VR software is possible by introducing an optimized workflow. In the present work, we developed a workflow for the visualization of the critical quality attribute (cQA) cell distribution in bioprinted (extrusion-based) samples in VR. The cQA cell distribution is directly influenced by the pre-processing step mixing of cell material in the bioink. Magnetic Resonance Imaging (MRI) was used as an analytical tool to generate spatially resolved 2.5 and 3D data of the bioprinted objects. A sample with poor quality in respect of the cQA cell distribution was identified as its inhomogeneous cell distribution could be displayed spatially resolved in VR. The described workflow facilitates the usage of VR as a tool for quality inspection in the field of bioprinting and represents a powerful tool for visualization of complex 3D MRI data.
Pilot-Scale Cultivation of the Snow Alga Chloromonas typhlos in a Photobioreactor
Authors: Schoeters Floris , Spit Jornt , Azizah Rahmasari Nur , Van Miert Sabine
Published: June 2022

The most studied and cultivated microalgae have a temperature optimum between 20 and 35°C. This temperature range hampers sustainable microalgae growth in countries with colder periods. To overcome this problem, psychrotolerant microalgae, such as the snow alga Chloromonas typhlos, can be cultivated during these colder periods. However, most of the research work has been carried out in the laboratory. The step between laboratory-scale and large-scale cultivation is difficult, making pilot-scale tests crucial to gather more information. Here, we presented a successful pilot-scale growth test of C. typhlos. Seven batch mode growth periods were compared during two longer growth tests in a photobioreactor of 350 L. We demonstrated the potential of this alga to be cultivated at colder ambient temperatures. The tests were performed during winter and springtime to compare ambient temperature and sunlight influences. The growth and CO2 usage were continuously monitored to calculate the productivity and CO2 fixation efficiency. A maximum dry weight of 1.082 g L−1 was achieved while a maximum growth rate and maximum daily volumetric and areal productivities of 0.105 d−1, 0.110 g L−1 d−1, and 2.746 g m−2 d−1, respectively, were measured. Future tests to optimize the cultivation of C. typhlos and production of astaxanthin, for example, will be crucial to explore the potential of biomass production of C. typhlos on a commercial scale.
The Intimate Connection Between Lipids and Hedgehog Signaling
Authors: Nguyen Thi D. , Truong Melissa E. , Reiter Jeremy F.
Published: June 2022

Hedgehog (HH) signaling is an intercellular communication pathway involved in directing the development and homeostasis of metazoans. HH signaling depends on lipids that covalently modify HH proteins and participate in signal transduction downstream. In many animals, the HH pathway requires the primary cilium, an organelle with a specialized protein and lipid composition. Here, we review the intimate connection between HH signaling and lipids. We highlight how lipids in the primary cilium can create a specialized microenvironment to facilitate signaling, and how HH and components of the HH signal transduction pathway use lipids to communicate between cells.
Unconventional Protein Secretion Dependent on Two Extracellular Vesicles: Exosomes and Ectosomes
Authors: Meldolesi Jacopo
Published: June 2022

In addition to conventional protein secretion, dependent on the specific cleavage of signal sequences, proteins are secreted by other processes, all together called unconventional. Among the mechanisms operative in unconventional secretion, some are based on two families of extracellular vesicle (EVs), expressed by all types of cells: the exosomes (before secretion called ILVs) and ectosomes (average diameters ∼70 and ∼250 nm). The two types of EVs have been largely characterized by extensive studies. ILVs are assembled within endocytic vacuoles by inward budding of small membrane microdomains associated to cytosolic cargos including unconventional secretory proteins. The vacuoles containing ILVs are called multivesicular bodies (MVBs). Upon their possible molecular exchange with autophagosomes, MVBs undergo two alternative forms of fusion: 1. with lysosomes, followed by large digestion of their cargo molecules; and 2. with plasma membrane (called exocytosis), followed by extracellular diffusion of exosomes. The vesicles of the other type, the ectosomes, are differently assembled. Distinct plasma membrane rafts undergo rapid outward budding accompanied by accumulation of cytosolic/secretory cargo molecules, up to their sewing and pinching off. Both types of EV, released to the extracellular fluid in their complete forms including both membrane and cargo, start navigation for various times and distances, until their fusion with target cells. Release/navigation/fusion of EVs establish continuous tridimensional networks exchanging molecules, signals and information among cells. The proteins unconventionally secretedviaEVs are a few hundreds. Some of them are functionally relevant (examples FADD, TNF, TACE), governing physiological processes and important diseases. Such proteins, at present intensely investigated, predict future discoveries and innovative developments, relevant for basic research and clinical practice.
Comparative Single-Cell Transcriptomics Reveals Novel Genes Involved in Bivalve Embryonic Shell Formation and Questions Ontogenetic Homology of Molluscan Shell Types
Authors: Salamanca-Díaz David A. , Ritschard Elena A. , Schmidbaur Hannah , Wanninger Andreas
Published: June 2022

Mollusks are known for their highly diverse repertoire of body plans that often includes external armor in form of mineralized hardparts. Representatives of the Conchifera, one of the two major lineages that comprises taxa which originated from a uni-shelled ancestor (Monoplacophora, Gastropoda, Cephalopoda, Scaphopoda, Bivalvia), are particularly relevant regarding the evolution of mollusk shells. Previous studies have found that the shell matrix of the adult shell (teleoconch) is rapidly evolving and that the gene set involved in shell formation is highly taxon-specific. However, detailed annotation of genes expressed in tissues involved in the formation of the embryonic shell (protoconch I) or the larval shell (protoconch II) are currently lacking. Here, we analyzed the genetic toolbox involved in embryonic and larval shell formation in the quagga mussel Dreissena rostriformis using single cell RNA sequencing. We found significant differences in genes expressed during embryonic and larval shell secretion, calling into question ontogenetic homology of these transitory bivalve shell types. Further ortholog comparisons throughout Metazoa indicates that a common genetic biomineralization toolbox, that was secondarily co-opted into molluscan shell formation, was already present in the last common metazoan ancestor. Genes included are engrailed, carbonic anhydrase, and tyrosinase homologs. However, we found that 25% of the genes expressed in the embryonic shell field of D. rostriformis lack an ortholog match with any other metazoan. This indicates that not only adult but also embryonic mollusk shells may be fast-evolving structures. We raise the question as to what degree, and on which taxonomic level, the gene complement involved in conchiferan protoconch formation may be lineage-specific or conserved across taxa.
Functional Dissection of Protein Kinases in Sexual Development and Female Receptivity of Drosophila
Authors: Chen Jiangtao , Zhu Huan , Wang Rong , Su Xiangbin , Ruan Zongcai , Pan Yufeng , Peng Qionglin
Published: June 2022

Protein phosphorylation is crucial for a variety of biological functions, but how it is involved in sexual development and behavior is rarely known. In this study, we performed a screen of RNA interference targeting 177 protein kinases in Drosophila and identified 13 kinases involved in sexual development in one or both sexes. We further identified that PKA and CASK promote female sexual behavior while not affecting female differentiation. Knocking down PKA or CASK in about five pairs of pC1 neurons in the central brain affects the fine projection but not cell number of these pC1 neurons and reduces virgin female receptivity. We also found that PKA and CASK signaling is required acutely during adulthood to promote female sexual behavior. These results reveal candidate kinases required for sexual development and behaviors and provide insights into how kinases would regulate neuronal development and physiology to fine tune the robustness of sexual behaviors.
Mitochondrial-Targeted Ratiometric Fluorescent Probe to Monitor ClO− Induced by Ferroptosis in Living Cells
Authors: Feng Beidou , Wang Kui , Wang Zhe , Niu Huiyu , Wang Ge , Chen Yuehua , Zhang Hua
Published: June 2022

Ferroptosis is a type of iron-dependent programmed cell death. Once such kind of death occurs, an individual cell would undergo a series of changes related to reactive oxygen species (ROS) in mitochondria. A mitochondrial-targeted ratiometric fluorescent probe (MBI-OMe) was developed to specifically detect ferroptosis-induced ClO−, whose recognition group is p-methoxyphenol, and the mitochondrial-targeted group is benzimidazole. The fluorescence of MBI-OMe was first quenched by 30 μM of Fe3+, and then MBI-OMe appeared as a ratiometric signal at 477 nm and 392 nm in response to ferroptosis-induced ClO− in living cells. MBI-OMe was successfully used to evaluate changes in ClO− induced by ferroptosis.
Automated Machine Learning for the Early Prediction of the Severity of Acute Pancreatitis in Hospitals
Authors: Yin Minyue , Zhang Rufa , Zhou Zhirun , Liu Lu , Gao Jingwen , Xu Wei , Yu Chenyan , Lin Jiaxi , Liu Xiaolin , Xu Chunfang , Zhu Jinzhou
Published: June 2022

Background

Machine learning (ML) algorithms are widely applied in building models of medicine due to their powerful studying and generalizing ability. This study aims to explore different ML models for early identification of severe acute pancreatitis (SAP) among patients hospitalized for acute pancreatitis.

Methods

This retrospective study enrolled patients with acute pancreatitis (AP) from multiple centers. Data from the First Affiliated Hospital and Changshu No. 1 Hospital of Soochow University were adopted for training and internal validation, and data from the Second Affiliated Hospital of Soochow University were adopted for external validation from January 2017 to December 2021. The diagnosis of AP and SAP was based on the 2012 revised Atlanta classification of acute pancreatitis. Models were built using traditional logistic regression (LR) and automated machine learning (AutoML) analysis with five types of algorithms. The performance of models was evaluated by the receiver operating characteristic (ROC) curve, the calibration curve, and the decision curve analysis (DCA) based on LR and feature importance, SHapley Additive exPlanation (SHAP) Plot, and Local Interpretable Model Agnostic Explanation (LIME) based on AutoML.

Results

A total of 1,012 patients were included in this study to develop the AutoML models in the training/validation dataset. An independent dataset of 212 patients was used to test the models. The model developed by the gradient boost machine (GBM) outperformed other models with an area under the ROC curve (AUC) of 0.937 in the validation set and an AUC of 0.945 in the test set. Furthermore, the GBM model achieved the highest sensitivity value of 0.583 among these AutoML models. The model developed by eXtreme Gradient Boosting (XGBoost) achieved the highest specificity value of 0.980 and the highest accuracy of 0.958 in the test set.

Conclusions

The AutoML model based on the GBM algorithm for early prediction of SAP showed evident clinical practicability.
Therapeutic Potential and Safety of the Cinnamomum zeylanicum Methanolic Extract Against Chronic Toxoplasma gondii Infection in Mice
Authors: Alanazi Abdullah D. , Almohammed Hamdan I.
Published: June 2022

Background

This experimental study determined the in vitro, in vivo, and toxicity effects of Cinnamomum zeylanicum methanolic extract (CZME) against Toxoplasma gondii infection.

Methods

The in vitro activity of CZME T. gondii tachyzoites was studied by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Infected mice were treated with CZME for two weeks at doses of 20, 40, and 60 mg/kg/day. Then, the therapeutic effects of CZME were evaluated by assessing the mean number and mean size of T. gondii tissue cysts, oxidant-antioxidant enzymes, pro-inflammatory cytokines, and mRNA expression levels of bradyzoite surface antigen 1 (BAG1) by real-time PCR.

Results

CZME significantly (p <0.001) increased the mortality rate of parasites in a dose- and time-dependent response. The mean number of intracellular tachyzoites was significantly reduced after CZME therapy. The treatment of infected mice with CZME resulted in a significant (p <0.001) downregulation of BAG1 and the level of lipid peroxidation (LPO) and nitric oxide (NO) as oxidative stress markers. However, a considerable rise (p <0.05) was found in the levels of antioxidant markers such as glutathione peroxidase (GPx), catalase enzyme (CAT), and superoxide dismutase enzyme activity (SOD). In a dose-dependent response, after treatment of infected mice with CZME, the level of pro-inflammatory cytokines of IFN-γ, IL-1β, and IL-12 was considerably elevated. CZME had no significant cytotoxicity on Vero cells, with a 50% cytotoxic concentration of 169.5 ± 5.66 μg/ml.

Conclusion

The findings confirmed the promising therapeutic effects of CZME on chronic toxoplasmosis in mice. Nevertheless, further investigations must confirm these results, elucidate its precise mechanisms, and examine its effectiveness in human volunteers.
Association of Healthy Lifestyle and Life Expectancy in Patients With Cardiometabolic Multimorbidity: A Prospective Cohort Study of UK Biobank
Authors: Cheng Xunjie , Ouyang Feiyun , Ma Tianqi , Luo Yi , Yin Jinghua , Li Jinchen , Zhang Guogang , Bai Yongping
Published: June 2022

Background

The prevalence of cardiometabolic multimorbidity (CMM), which significantly increases the risk of mortality, is increasing globally. However, the role of healthy lifestyle in the secondary prevention of CMM is unclear.

Methods

In total, 290,795 participants with CMM, which was defined as coexistence of at least two of hypertension (HTN), diabetes mellitus (DM), coronary heart disease (CHD), and stroke (ST), and those without these four diseases at baseline were derived from UK Biobank. The associations between specific CMM patterns and mortality, and that between healthy lifestyle (including physical activity, smoking, alcohol consumption, and vegetable and fruit consumption) and mortality in patients with specific CMM patterns were calculated using the flexible parametric Royston-Parmar proportion-hazard model. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated.

Results

During a median 12.3-year follow up period, 15,537 (5.3%) deaths occurred. Compared with participants without cardiometabolic diseases, the HRs for all-cause mortality were 1.54 [95% confidence interval (CI): 1.30, 1.82] in participants with HTN + DM, 1.84 (95% CI: 1.59, 2.12) in those with HTN + CHD, 1.89 (95% CI: 1.46, 2.45) in those with HTN + ST, and 2.89 (95% CI: 2.28, 3.67) in those with HTN + DM + CHD. At the age of 45 years, non-current smoking was associated with an increase in life expectancy by 3.72, 6.95, 6.75, and 4.86 years for participants with HTN + DM, HTN + CHD, HTN + ST, and HTN + DM + CHD, respectively. A corresponding increase by 2.03, 1.95, 2.99, and 1.88 years, respectively, was observed in participants with regular physical activity. Non-/moderate alcohol consumption and adequate fruit/vegetable consumption were not significantly associated with life expectancy in patients with specific CMM patterns.

Conclusion

Cardiometabolic multimorbidity was associated with an increased risk of mortality. Regular physical activity and non-current smoking can increase life expectancy in patients with specific CMM patterns.
Copy Number Analyses Identified a Novel Gene: APOBEC3A Related to Lipid Metabolism in the Pathogenesis of Preeclampsia
Authors: Liu Nan , Guo Yu-Na , Wang Xiao-Jin , Ma Jue , He Yun-Ting , Zhang Fang , He Hao , Xie Jin-Liang , Zhuang Xu , Liu Meng , Sun Jian-Hua , Chen Yan , Lin Jian-Hua , Gong Li-Kun , Wang Bing-Shun
Published: June 2022

Background

Preeclampsia is a heterogeneous and complex disease with its pathogenesis mechanism not fully elucidated. A certain subset of patients with preeclampsia exhibit disturbances in lipid metabolism before clinical symptoms. Moreover, there is a tendency for preeclampsia to run in families. Whether genetic factors play a role in abnormal lipid metabolism during the incidence of preeclampsia has not been well investigated.

Methods

Preeclampsia patients (n = 110) and healthy age- and gravidity-matched pregnant women (n = 110) were enrolled in this study. Peripheral blood specimens were used for genomic analysis (n = 10/group) or laboratory validation (n = 100/group). We retrospectively obtained the baseline clinical characteristics of 68 preeclampsia patients and 107 controls in early pregnancy (12–14 gestational weeks). Correlation analyses between differential genes and baseline lipid profiles were performed to identify candidate genes. In vitro and in vivo gain-of-function models were constructed with lentivirus and adeno-associated virus systems, respectively, to investigate the role of candidate genes in regulating lipid metabolism and the development of preeclampsia.

Results

We observed that preeclampsia patients exhibited significantly elevated plasma TC (P = 0.037) and TG (P < 0.001) levels and increased body mass index (P = 0.006) before the disease onset. Within the region of 27 differential copy number variations, six genes potentially connected with lipid metabolism were identified. The aberrant copies of APOBEC3A, APOBEC3A_B, BTNL3, and LMF1 between preeclampsia patients and controls were verified by quantitative polymerase chain reaction. Especially, APOBEC3A showed a significant positive correlation with TC (P < 0.001) and LDL (P = 0.048) in early pregnancy. Then, our in vitro data revealed that overexpression of APOBEC3A disrupted lipid metabolism in HepG2 cells and affected both cholesterol and fatty acid metabolisms. Finally, in vivo study in a hepatic-specific overexpressed APOBEC3A mouse model revealed abnormal parameters related to lipid metabolism. Pregnant mice of the same model at the end of pregnancy showed changes related to preeclampsia-like symptoms, such as increases in sFlt-1 levels and sFlt-1/PLGF ratios in the placenta and decreases in fetal weight.

Conclusion

Our findings established a new link between genetics and lipid metabolism in the pathogenesis of preeclampsia and could contribute to a better understanding of the molecular mechanisms of preeclampsia.
Direct Oral Anticoagulants vs. Warfarin in Hemodialysis Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis
Authors: Elfar Sohil , Elzeiny Sara Mohamed , Ismail Hesham , Makkeyah Yahya , Ibrahim Mokhtar
Published: June 2022

Background

The use of Direct Oral Anticoagulants (DOACs) in patients who have both atrial fibrillation (AF) and end-stage renal disease (ESRD) requiring hemodialysis remains controversial, with warfarin remaining the mainstay of the treatment. As hemodialysis patients were excluded from most clinical DOACs trials, the evidence of their efficacy and safety is lacking in this cohort of patients.

Aim

To review the current evidence investigating safety profile and the efficacy of DOACs in comparison with warfarin in patients with AF and end-stage renal disease (ESRD) requiring hemodialysis.

Methods and Results

We included five studies with a total of 34,516 patients in our meta-analysis. The outcomes were major bleeding, ischemic stroke, systemic embolization, hemorrhagic stroke, gastrointestinal bleeding, minor bleeding, and death. Of these patients, 31,472 (92.14%) received warfarin and 3,044 patients received DOACs (8.91%). No significant differences in the incidence of hemorrhagic stroke, major bleeding, hemodialysis access site bleeding, ischemic stroke, and GI bleeding were found between DOACs and warfarin. However, there were higher rates of systemic embolization, minor bleeding, and death events in patients who received DOACs than in the warfarin group (3.39% vs. 1.97%, P-value = 0.02), (6.78% vs. 2.2%, P-value 0.02), and (11.38% vs. 5.12%, P-value < 0.006) respectively.

Conclusion

In patients on dialysis who require anticoagulation for AF, warfarin could be associated with a significant reduction in minor bleeding, systemic embolization, and death compared to DOACs. These findings need to be validated by further prospective studies to address the best strategy to deal with the increased thrombotic and bleeding risks in such patients.
Pathogenetic Link of Cardiac Rupture and Left Ventricular Thrombus Following Acute Myocardial Infarction: A Joint Preclinical and Clinical Study
Authors: Ma Shan , Bai Ling , Liu Ping , She Gang , Deng Xiu-Ling , Song An-Qi , Du Xiao-Jun , Lu Qun
Published: June 2022

Background

Cardiac rupture (CR) and left ventricular thrombus (LVT) remain important complications of acute myocardial infarction (MI), and they are currently regarded as independent events. We explored the pathogenetic link between CR and LVT by investigating a murine model of MI with a high frequency of CR and in patients with acute MI.

Methods

MI was induced in mice, the onset of CR was monitored, and the hearts of mice with or without fatal CR were histologically examined. Between 2015 and 2022, from patients admitted due to acute MI, the data of patients with CR or LVT were retrospectively collected and compared to uncomplicated patients (control).

Results

A total of 75% of mice (n = 65) with MI developed CR 2–4 days after MI. A histological examination of CR hearts revealed the existence of platelet-rich intramural thrombi in the rupture tunnel, which was connected at the endocardial site to platelet-fibrin thrombi within an LVT. In CR or non-CR mouse hearts, LV blood clots often contained a portion of platelet-fibrin thrombi that adhered to the infarct wall. In non-CR hearts, sites of incomplete CR or erosion of the infarct wall were typically coated with platelet thrombi and dense inflammatory cells. Of 8,936 patients with acute MI, CR and LVT occurred in 102 (1.14%) and 130 (1.45%) patients, respectively, with three cases having both complications. CR accounted for 32.8% of in-hospital deaths. The majority of CR (95%) or LVT (63%, early LVT) occurred within 7 days. In comparison to the control or LVT-late groups, patients with CR or early LVT reported increased levels of cellular and biochemical markers for inflammation or cardiac injury.

Conclusion

CR and LVT after MI are potentially linked in their pathogenesis. LVT occurring early after MI may be triggered by a thrombo-inflammatory response following wall rupture or endocardial erosion.