bluuebunny/crossref_metadata_2025 huggingface dataset:
PENERAPAN PEMBELAJARAN BERDIFERENSIASI BERDASARKAN ASPEK KESIAPAN BELAJAR SISWA SEKOLAH MENENGAH ATAS
Authors: Karmilawati Karmilawati , T Ahmad Yani
Published: December 2024

ABSTRAKGuru menghadapi berbagai tantangan dalam menentukan strategi dan pendekatan pembelajaran yang mampu memenuhi kebutuhan belajar siswa, yang mencakup kesiapan belajar, profil individu, dan minat mereka. Salah satu metode efektif untuk menangani keragaman kebutuhan ini adalah penerapan pembelajaran berdiferensiasi. Metode ini memungkinkan guru untuk menyesuaikan proses pembelajaran agar setiap siswa, dengan berbagai karakteristiknya, dapat belajar secara optimal. Artikel ini bertujuan untuk mengidentifikasi manfaat yang diperoleh dari implementasi pembelajaran berdiferensiasi berdasarkan tingkat kesiapan belajar siswa. Penelitian dilakukan dengan pendekatan deskriptif analitis berbasis kualitatif, di mana data dikumpulkan melalui observasi yang dilakukan selama kegiatan pembelajaran di kelas.Hasil penelitian menunjukkan bahwa penerapan pembelajaran berdiferensiasi berdasarkan tingkat kesiapan belajar siswa memberikan dampak positif, baik untuk siswa maupun guru. Dampak tersebut meliputi: (1) Semua siswa, terlepas dari perbedaan tingkat kesiapan mereka, mampu mengikuti proses pembelajaran dengan baik; (2) Siswa mengalami peningkatan rasa percaya diri, yang mendorong mereka untuk lebih aktif dan termotivasi dalam belajar.Kata Kunci: Pembelajaran berdiferensiasi, Kebutuhan Belajar, Kesiapan BelajarABSTRACTTeachers face various challenges in determining learning strategies and approaches that are able to meet students' learning needs, which include their learning readiness, individual profiles and interests. One effective method for dealing with this diversity of needs is the application of differentiated learning. This method allows teachers to adjust the learning process so that each student, with their various characteristics, can learn optimally. This article aims to identify the benefits obtained from implementing differentiated learning based on the student's level of learning readiness. The research was carried out using a qualitative-based analytical descriptive approach, where data was collected through observations made during classroom learning activities. The results of the research showed that the application of differentiated learning based on students' level of learning readiness had a positive impact, both for students and teachers. These impacts include: (1) All students, regardless of differences in their level of readiness, are able to follow the learning process well; (2) Students experience increased self-confidence, which encourages them to be more active and motivated in learning.Keywords: Differentiated Learning, Learning Needs, Learning Readiness
Pengaruh Digital Marketing dan Customer Relationship Marketing Terhadap Customer Loyalty Pada Laughing Buddha Bar Ubud
Authors: Suryawan Tjokorda Gde Agung Wijaya Kesuma , Purwati Ni Kadek Enny , Handayani Made Mulia , Meryawan I Wayan
Published: December 2024

Customer Loyalty atau Loyalitas Pelanggan merupakan upaya untuk menciptakan dan mempertahankan pelanggan. Perusahaan perlu mengetahui sejauh mana mereka memiliki Loyalitas Pelanggan dan melakukan upaya untuk meningkatkannya. Beberapa faktor dalam mengoptimalkan Loyalitas Pelanggan di Laughing Buddha Bar adalah melalui Digital Marketing dan penerapan Customer Relationship Marketing. Tujuan dari penelitian ini adalah untuk mengetahui pengaruh secara parsial dan simultan Digital Marketing dan Customer Relationship Marketing terhadap Customer Loyalty di Laughing Buddha Bar di Ubud. Penelitian ini menggunakan metode Accidental Sampling dengan jumlah sampel sebanyak 96 responden. Metode ini dilakukan dengan memilih responden yang ditemui pada saat penelitian, dan menggunakan metode kuantitatif dengan jenis penelitian survei. Teknik pengumpulan data yang digunakan meliputi observasi, wawancara, angket dan studi dokumentasi. Seluruh data dianggap valid dan reliabel dengan uji instrumen penelitian (uji validitas dan uji reliabilitas) kemudian dapat dianalisis dengan menggunakan analisis regresi linier berganda, analisis koefisien determinasi, dan uji hipotesis (uji t dan uji F). Hasil penelitian menunjukkan bahwa terdapat pengaruh positif dan signifikan baik secara parsial maupun simultan antara Digital Marketing dan Customer Relationship Marketing terhadap Customer Loyalty di Laughing Buddha Bar di Ubud.
Pengaruh Remunerasi terhadap Kualitas Pelayanan dan Turnover Intention Dokter Spesialis di RSUD Sultan Imanuddin Pangkalan Bun
Authors: Lazuardy Muhammad Azhary , Hidayat Dasrun , Bagenda Wahyuddin
Published: December 2024

Rumah sakit sangat bergantung pada kinerja sumber daya manusia (SDM) untuk operasional yang efektif. Manajemen SDM yang efisien membantu merekrut dan mempertahankan tenaga kerja terampil. Remunerasi kompetitif berperan penting dalam meningkatkan motivasi, kepuasan, dan loyalitas, yang memengaruhi kualitas layanan serta niat untuk keluar (turnover intention). Penelitian ini menganalisis pengaruh remunerasi terhadap kualitas layanan dan niat untuk keluar di kalangan dokter spesialis RSUD Sultan Imanuddin, Pangkalan Bun. Penelitian menggunakan desain cross-sectional dengan survei total sampling. Dari 42 dokter spesialis, 39 berpartisipasi. Analisis data dilakukan menggunakan metode SEM-PLS. Hasil penelitian menunjukkan bahwa gaji dan tunjangan (remunerasi) tidak memiliki pengaruh signifikan terhadap kualitas layanan (koefisien jalur -0,008, p>0,05). Namun, remunerasi secara signifikan memengaruhi niat untuk keluar (koefisien jalur -0,675, p<0,05), di mana remunerasi yang lebih rendah meningkatkan kemungkinan dokter untuk keluar. Meskipun demikian, niat untuk keluar tidak memiliki pengaruh signifikan terhadap kualitas layanan (koefisien jalur 0,119, p>0,05), dan remunerasi yang rendah tidak secara langsung memengaruhi kualitas layanan (koefisien jalur -0,081, p>0,05). Remunerasi berdampak pada niat untuk keluar tetapi tidak pada kualitas layanan. Rumah sakit perlu mengeksplorasi faktor lain yang memengaruhi kualitas layanan serta menerapkan kebijakan remunerasi yang adil, transparan, dan kompetitif untuk mempertahankan dokter spesialis berkualitas tinggi.
Internet kot orodje razvoja sodobne družbe
Authors: Strašek Nejc
Published: December 2024

Internet je globalno omrežje, ki omogoča komunikacijo, izmenjavo informacij in dostop do številnih virov. Sestavljen je iz milijard naprav, povezanih med seboj, kar omogoča prenos podatkov v realnem času. Rojstvo in hitra rast uporabe interneta sta postala ena najpomembnejših prelomnic sodobnega časa. Razširil se je na vse konce sveta in postal najhitreje rastoči medij, ki je nepogrešljiv pri praktično vseh naših vsakodnevnih opravilih. Prav zaradi njegove vsakodnevne uporabe smo se odločili raziskati zgodovino njegovega nastanka, razvoj ter storitve in uporabo interneta v sodobnem času. Dosegel je izredno rast, število uporabnikov pa se iz dneva v dan povečuje. Aprila 2024 je bilo po vsem svetu 5,44 milijarde uporabnikov interneta, kar predstavlja 67,1 % svetovnega prebivalstva. S svojo neprekinjeno rastjo je internet postal nepogrešljiv del sodobne družbe, ki je spremenil način, kako delujemo, se povezujemo in živimo.
Leadership positions of Russian theoretical and educational schools of journalism
Authors:   Saint Petersburg State University, Korkonosenko Sergey G. , Berezhnaia Marina A. ,   Saint Petersburg State University, Khubetcova Zalina F. ,   Saint Petersburg State University
Published: December 2024

The article examines the current state of Russian theoretical and educational schools of journalism in the context of global trends in the development of journalistic education. The authors critically assess the established methodology for building international university rankings, which, according to a number of parameters, is not able to identify the achievements and advantages of Russian universities. It is necessary to abandon the monocentric coordinate system in favor of a polycentric methodology. In this case, opportunities open up for the productive use of a cultural and civilizational approach, which involves the analysis of journalistic education in genetic relationship with the cultural environment in general and national journalism with its stable features in particular. From the above positions, the Russian practice of training journalistic personnel is organically related to the concept of theoretical and educational schools, which to a much lesser extent can be attributed to the practice of many universities abroad. It implies in-depth academic training with strong social and humanitarian accents, the ideological and conceptual originality of each of the schools, the presence of recognized leaders and the continuation of their initiatives in the works of their followers, providing teaching with fundamental educational publications and, in turn, inseparable interaction with the professional industry. Russian journalism schools have a number of properties and achievements that are not typical for other national educational models, and act as leaders in the corresponding parameters. To confirm these assumptions, it is necessary to conduct a special comprehensive study. The “Theoretical and Pedagogical Schools of Journalism in Russia” research project, implemented at St. Petersburg State University, is aimed at solving these problems. The project program includes the reconstruction of the preconditions and main milestones in the history of journalistic education in Russia, a structural and functional analysis of the current conditions, the creation of a portrait gallery of the founders and outstanding representatives of schools in the country's universities.
The role of social and humanitarian expertise in ensuring the scientific leader-ship of the Russian Federation
Authors:   Lomonosov Moscow State University, Bryzgalina Elena V. , Kiselev Vladimir N. ,   Lomonosov Moscow State University
Published: December 2024

This article considers the scientific leadership of the state as a manifestation of the ability to independently determine scientific policy, protect the scientific and technological sphere from the standards of activity being imposed from outside, and promote the na-tional value matrix by influencing the mecha-nisms for regulating the global circulation of innovative products and services. The concep-tual basis and practice of social and humani-tarian expertise bases on interdisciplinary support of all stages of scientific and techno-logical solutions in high-risk areas. Social and humanitarian expertise is necessary in pro-jects where the emergence of innovative ob-jects and new social relations, the emergence of value conflicts and ethical dilemmas are expected. As described in the article, exper-tise has an internal and external vector. The methodological features of the social and hu-manitarian discipline are associated in the ar-ticle with the “Collingridge dilemma”. Among the tasks of social and humanitarian expertise to ensure scientific leadership, the article highlights the following statements: at the in-ternational level – the development of ethi-cal and legal standards for the regulation of scientific and technological products; at the national level – a systemic understanding of value orientations that affect socio-technical development and are updated with the intro-duction of new products and technologies; creation of a mechanism to legitimize state policy in the science and technology devel-opment; creation of real mechanisms to inte-grate specialists in social, humanitarian, and natural sciences, technical specialties and business representatives. The article substan-tiates the connection between the develop-ment of social and humanitarian expertise and the policy of incrementalism in relation to in-novations. Among the factors that can nega-tively affect the realization of the potential of social and humanitarian expertise to ensure scientific and technological leadership at the state level, the authors refer to the lack of legislative consolidation of the status of social and humanitarian expertise, the dominance of competitive relations against the background of the commercialization of science, and the dependence of expert positions on adminis-trative and economic conditions and subject standards.
Scientific leadership and the position of the early career scientist in the social hierarchy of research teams
Authors:   Institute of Philosophy, Russian Academy of Sciences, Pirozhkova Sophia V.
Published: December 2024

The article aims to analyze the concept of “youth scientific leadership” – clarifying its content, its relevance to the realities of the organization of the scientific process and the characteristics of the phenomenon that it is designed to fix. For this purpose, the study consistently reveals the content of the phe-nomena of leadership and scientific leader-ship and critically evaluates the existing theo-retical approaches to their definition. Based on the analysis of research on scientific lead-ership and practical developments in the field of scientific policy, the author concludes that today the understanding of scientific leader-ship is ambivalent. On the one hand, it is in-terpreted as the achievement of outstanding scientific results, which allows indirectly in-fluencing colleagues and the development of a separate or several scientific areas, as well as directly influencing them by referring to scientific, organizational and teaching activi-ties. On the other hand, leadership is inter-preted in a managerialism spirit – as a set of competencies and appropriate tools that al-low achieving efficiency in the management of the group. At the same time, according to the basic documents in the field of personnel training and personnel policy developed in the European Union, leadership in science is understood not as an exceptional position, but as the final stage of the development of a scientific career. Based on this, a young scien-tist whose status is set not by age, but by be-ing at the initial stages of professional devel-opment, cannot be a scientific leader by defi-nition. The author offers a solution to this conflict and shows how the antithesis of intel-lectual and creative leadership and leader-ship, understood in a managerial spirit, mani-fests itself when it comes to scientists taking the first steps in their profession.
Innovative forms of caritative activity: secular and spiritual hybridity of crowd-funding
Authors:   Vladimir Law Institute of the Federal Penitentiary Service, Semenov Ivan A.
Published: December 2024

Based on a comparison of secular and spiritual approaches to charitable activities (using crowdfunding as an example), the article ar-gues that acts of web-charity are predomi-nantly hybrid in nature. This is due, firstly, to the historical development of caritative activ-ity, which has evolved in the paradigm of the theocentric institution of Christian denomina-tions. Today, according to the author, reli-gious web-charity is characterized by a directive and patriarchal nature. Having a canonical pattern, spiritual caritative activity has some signs of institutionalization, which is expressed in an attempt to bring web-charity under general rules, set the algorithm of ap-plication of the mentioned platforms and de-termine imperatively the circle of subjects with the right to use charitable crowdfunding. Second, the increased role of digitalization not only dictates a certain vector of develop-ment, but also forms a trend toward digital socio-economic relations, which rely on a lib-eral approach to caritative activity and imply «free relations», that is, recipient-donor in-teraction not bound by additional obligations. Both approaches to the implementation of digital charitable activities have their pros and cons: analyzing them, the author concludes about the importance of a hybrid approach and mixed beginnings of web-charity. The suc-cessful implementation of hybridization of in-novative forms of caring activities and their introduction into practice significantly in-creases the speed of solving financial problems related to fundraising, as well as the completeness of coverage of the audience in-terested in caring, while the institutional side of hybridization allows unifying and structur-ing caring projects.
The chaos axiology in the context of theoretical ethics
Authors:   Russian Federal Nuclear Center – All-Russia Research Institute of Experimental Physics, Kanunov Anton E.
Published: December 2024

The purpose of this paper is to actualize the concept of “chaos” explicated within theoret-ical ethics and study the relationship thereof with a moral act phenomenon. The paper consists of three parts. The first part contains the formulation of the research problem. The author herein relies on the statement sup-ported by some researchers, thereunder an individual is an open, synergistic and highly non-equilibrium system with a dissipative structure of behavior. The second part deals with the consideration of the “chaos – cos-mos” opposition, wherein in view of binary logic the chaos is endowed with a solely nega-tive meaning as contrasted with the cosmos. Such an interpretation is associated, first of all, with the prevalence of mechanical sys-temicity and linear determinism in classical rationalism and a relevant type of worldview. The principles of non-classical dialectics pro-mote the destruction of this binary opposition and define the chaos as the most important component in the development of systems of any nature. The third part considers the prop-erties of chaotic systems in their conceptual and functional relationship with the proper-ties of an act as the core of the ethical do-main. The internal act structure is thereat presented as a complex alternation of self-organization (the forming-up of the order out of the chaos) and the chaotization (the chaos emergence from the order). Such an approach implies in ethics the “inclusion” of new com-plex phenomena in the subject of its study and takes into account the heterogeneity of the ethical domain and the essential complex-ity of the morality subject reflected mainly in the act.
“Futures literacy” or “literacy in relation to the future” as an academic discipline in the modern information society
Authors:   SEI HPT Gorlovka University for Foreign Languages, Rochnyak Elena V.
Published: December 2024

The article examines the facts of introducing the discipline “Futures literacy” into the edu-cational practice of various countries, explains the need for this innovation and reveals the basic characteristics of the concept of “litera-cy in relation to the future” through a com-parison of various definitions. The relevance of the article is due to the relative novelty of the topic (the key concept was introduced by UNESCO in 2012), as well as the insufficient number of scholarly research considering this phenomenon in the context of social philoso-phy. The purpose of the study is to form a generalized picture of the essence of the con-cept of “futures literacy” and its interpreta-tion in educational practice. The study em-phasizes that literacy in relation to the future is a universal skill to consciously meet changes and form them yourself, the development of which is a necessary condition for living in the society that we want to see in the future.
F. Bacon in the theory and history of scientific rationality and technogenic civilization
Authors:   National Research Lobachev-sky State University of Nizhni Novgorod, Maslov Vadim M. , Sorokin Roman V. ,   National Research Lobachevsky State University of Nizhni Novgorod
Published: December 2024

The high problematic nature of modern social life, directly related to intensive scientific and technological development, determines the fundamental nature of the theories of technogenic civilization and scientific (scientific and philosophical) rationality. The formation of a new, post-non-classical scientific rationality is an adequate response to the contemporary stage of technogenic civilization (taking into account the unavoidability of the value component of thought and the need for humanitarian expertise of scientific and technical realities and projects). A necessary direction for the further evolution of the theories of technogenic civilization and scientific rationality is the elaboration of an appropriate historical approach: the initial one in this case is the philosophy of F. Bacon. In terms of developingthe historical component of the theory of technogenic civilization, the well-known F. Bacon’s ideas about technogenicity are taken in a new, appropriate paradigm. F. Bacon must be approved as the first philosopher of Modern times in line with the general history of philosophy (the leading scientific/educational works on the history of philosophy from ancient times to the present day). In terms of the development of the historical component of the theory of scientific rationality, the authors show that F. Bacon's «Solomon’s House» was guided by a dialectically productive «closeness – openness». The closeness of the scientific community of F. Bacon provided an unhindered search for truth and benefit; openness – public approval and assistance. Direct arguments for the openness of the « Solomon’s House»: the openness of the «new organon» and the choice of the utopia genre for the presentation of the ideas of the «New Atlantis». In tune with modern technogenic realities and post-non-classical rationality F. Bacon's ideas are very radical (especially given the low competitiveness of scientists and philosophers compared to politicians and businessmen), which determined their historical and philosophical partial reflection. Further deepening into historical and philosophical problems is organically correlated with the solution of modern problems within the framework of the theories of technogenic civilization and scientific rationality. All these are directly related to the improvement of modern social and humanitarian education. The latter is worth emphasizing, since the prospects for the development of humanitarian expertise lead to the formation of a new form of university – an expert university.
Digital transformation of higher education and the phenomenon of deanthro-pologization
Authors:   Lomonosov Moscow State University, Davydov Igor A.
Published: December 2024

The article discusses aspects of the digital transition that is being intensively carried out in higher education. They affect not only the structural and functional elements of higher education, but also the most fundamental as-pects of anthropological discourse. Either dig-ital reality will replace the anthropological features of the educational environment, or it will open up new opportunities for human realization. Which line will ensure the most harmonious development of the student's personality? The purpose of the article is to explicate the basic ideas of the two discours-es, which largely determine the concepts of philosophical anthropology in the era of the digital turn. The first discourse, Kant's, repre-sents consciousness through its unity and striving from the analysis of phenomena to their synthesis. The second one, presented by object-oriented ontologists, demonstrates the mechanism of splitting reality through regres-sion to the digital structure, which is opposite to Kant's understanding of consciousness. The main idea of the author is that the last dis-course leaves no room for actualization of meanings that are absent in it a priori due to the presence of a nihilistic intention not only to the Heideggerian ontological, but also in relation to the ontic planes of being. Continu-ing the tradition of metaphysics, in which Be-ing understood non-consciously was subject to elimination, new ontologists form gaps in the description of consciousness. By that, in a sense, they are rolling back the achievements of scientific knowledge expressed by the con-cepts of quantum physics and Kant's philoso-phy, on which the author of the article relies. Aspects of the elimination of subjectivity from the environment of higher education in the era of the digital turn are shown by the ex-ample of the concepts of Spitzer, Strelnikova, teaching practice of Startsev, Dzhabrailov, Khlebnikov. The author comes to the conclu-sions that the anthropological discourse of the unity of consciousness can be overcome by returning the dominance of the category of number, a mathematically “verified” new materialism, within which complex deanthro-pologization is carried out through the priva-tion of access to the integral consciousness. Privation, in turn, is conditioned by the whole movement of European philosophy along the path of increasing the role of intel-ligence and knowledge, on the one hand, and decreasing the role of subjectivity, on the other. The realities of the digital transfor-mation of the higher education environment are a consequence of this movement of digital thinking.
On the cognitive potential of intuition (based on the example of the concepts of R. Descartes, B. Spinoza, and G. Leibniz)
Authors:   National Research Lobachev-sky State University of Nizhny Novgorod, Sokolova Olesya I.
Published: December 2024

Determining the role of intuition in the process of cognition is an urgent problem in modern science and philosophy. Scientific ideas about intuition are based on the assumption of the interaction between feelings, experience and reason in the process of obtaining knowledge. The research of intuition in modern philosophy relies on the definition of its ontological and epistemological characteristics, the formation of a new understanding of intuition, the identification of its place and role in the structure of cognition. One of the trends in studying the phenomenon of intuition in philosophy is the historical and philosophical direction (Asmus V.F., Sokolov V.V.), which allows us to turn to the search for meanings laid down by thinkers of the past in this concept and determine the role of the phenomenon of intuition in the process of achieving true knowledge. Using the method of comparative historical analysis allows us to identify periods of interpretation of intuition in the general context of the development of philosophical ideas and determine their uniqueness depending on a specific historical period. Philosophers adopt the shape of science – axiomatic structure of theory construction – and implement it for the expression of their philosophic views. R. Descartes was the first who formulated the statement that the axioms accepted without proof, or “provided by mind” intuitions, which should be considered the initial, starting points of knowledge. Subsequently, his doctrine about intuition and the types of reliable knowledge developed further in philosophical systems of B. Spinoza and G. Leibniz. The concept of intuition, which is opposite to sensory knowledge with its randomness, unreliability, importance of details, forms the basis of reliable, mathematical knowledge. Mathematical knowledge acts as the ideal which the rational scrutiny of the world should seek to reach. Comprehensive and necessary features of the axioms, the fundamental bases of knowledge are directly perceived by the forces of mind. At the same time, it was a real stumbling block to determine such unconditional knowledge bases. As such bases, R. Descartes regarded “inborn ideas”, B. Spinoza – intellectual intuitions, while G. Leibniz – initial properties of thinking. Conducting a historical and philosophical study of the concept of intuition in the context of the Modern era allows us to conclude about the cognitive potential of intuition, which consists in the further unfolding of knowledge as a deductive following from the first axiom to “lower truths”.
Dualism of technological progress and the dangerous practice of the anthropocene
Authors:   National Research Lobachevsky State University of Nizhni Novgorod, Sukhanova Elena V. , Burkow Artyom D. ,   National Research Lobachevsky State University of Nizhni Novgorod
Published: December 2024

The current article presents a study of various catastrophes and cataclysms that have accom-panied humanity throughout its history and significantly influenced the course of its eco-nomic and social changes. Albeit mostly natu-ral, they determined fates of many peoples and civilizations. With the further growth of technological achievements during the indus-trial revolution humanity began to be ex-posed to a range of hazards associated with anthropogenic risks. These include nano- and biotechnologies, artificial intelligence, nucle-ar war, threat of overpopulation and more. Widely considered to be relevant today are the ecological and climatic problems caused by industrial human activity in past two cen-turies. Therefore, the object of this study is technological progress in the context of the modern discourse of the Anthropocene. The purpose of the article is to research the con-tradictory nature of technology, varying be-tween utopian expectations of quality of life improvements and the negative consequenc-es of technological evolution. Achieving this goal requires solving a number of tasks, which include: studying the available narrative ma-terial in the historical and philosophical tradi-tion; analyzing the specifics of various theoret-ical concepts and their correlation with prac-tical transformations in nature and society; es-tablishing the relationship between natural disasters and anthropogenic crisis. Research novelty of the work lies in the establishment of a natural causal relationship between natu-ral disasters of the past and the modern crisis of the Anthropocene, with consideration of dangers of the predicted technological singu-larity as a consequence of the dialectic (dual-istic) development of technology. The authors conclude that due to the ever-increasing de-sire for prosperity and comfort, human society at the beginning of the XXI century came again to a turning point in its history, the result of which could be unprecedented global man-made catastrophe.
CMS121, a Novel Drug Candidate for the Treatment of Alzheimer’s Disease and Age-Related Dementia
Authors: Currais Antonio , Raschke William , Maher Pamela
Published: December 2024

Old age is the major risk factor for sporadic Alzheimer’s disease (AD). However, old age-related changes in brain physiology have generally not been taken into consideration in developing drug candidates for the treatment of AD. This is at least partly because the role of these age-related processes in the development and progression of AD are still not well understood. Nevertheless, we and others have described an association between the oxytosis/ferroptosis non-apoptotic regulated cell death pathway and aging. Based on this association, we incorporated protection against this pathway as part of a cell-based phenotypic screening approach to identify novel drug candidates for the treatment of AD. Using this approach, we identified the fisetin derivative CMS121 as a potent neuroprotective molecule that is able to maintain cognitive function in multiple pre-clinical models of AD. Furthermore, we identified a key target of CMS121 as fatty acid synthase, a protein which had not been previously considered in the context of AD. Herein, we provide a comprehensive description of the development of CMS121, its preclinical activities, and the results of the toxicology testing that led to its IND approval.
Pharmacodynamic and Clinical Effects of Ginkgo Biloba Extract EGb 761 and Its Phytochemical Components in Alzheimer’s Disease
Authors: Morató Xavier , Tartari Juan Pablo , Pytel Vanesa , Boada Mercè
Published: December 2024

Extracts made from plants are complex mixtures of substances with varying compositions depending on the plant material and method of manufacture. This complexity makes it difficult for scientists and clinicians to interpret findings from pharmacological and clinical research. We performed a narrative review summarizing information on ginkgo biloba leaf extract, its composition, pharmacological data and clinical evidence supporting its administration for the treatment of Alzheimer’s disease (AD). Medicinal products containing ginkgo biloba leaf extract which are manufactured in compliance with the requirements of the European Pharmacopoeia are approved as medicinal products for the treatment of dementia and related conditions by drug regulatory agencies in Europe, Asia and South America. As multicomponent mixtures, they may affect various targets in the pathogenesis of AD, the most common form of dementia. Pharmacodynamic studies demonstrate the effects of EGb 761 and individual constituents on various pathophysiological features of experimentally induced cognitive impairment and neurodegeneration that could contribute to its clinical efficacy. The safety and efficacy in the treatment of AD and cognitive decline has been studied in randomized, placebo-controlled clinical trials. Most of the studies that investigate the effects of ginkgo biloba extract (GbE) used the special extract EGb 761, which makes it the best-researched plant preparation worldwide. It is therefore the only herbal alternative to standard-of-care anti-dementia drugs. However, the mechanism of action has not been fully elucidated yet, and the clinical studies in AD show heterogeneity.
Growth Factor Gene Therapy for Alzheimer’s Disease
Authors: Tuszynski Mark H.
Published: December 2024

Nervous system growth factors are natural proteins of the brain that influence neuronal survival and function throughout life, from embryonic development to old age. In animal models of Alzheimer’s disease (AD), the growth factor brain derived neurotrophic factor (BDNF) prevents neuronal death, activates neuronal function, builds new synapses and improves learning and memory. Accordingly, we are determining whether gene delivery of BDNF in patients with AD will slow disease progression and improve memory. In a previous clinical trial of nerve growth factor (NGF) gene therapy in AD patients (NCT00017940, June 2001), we learned that growth factors can unequivocally elicit classic trophic responses from degenerating neurons in AD. Experience gained from the earlier NGF gene therapy trial is guiding our effort to optimize gene delivery of BDNF in our present clinical program (NCT05040217, June 2021).
Ketogenic Approaches for the Treatment of Alzheimer’s Disease
Authors: Gabuzyan Renata , Lee Christopher , Nygaard Haakon B.
Published: December 2024

Dementia represents one of the largest and most urgent public health problems across the globe. Modeling projections have estimated that delaying the onset of Alzheimer’s disease (AD) by 6 months would reduce the prevalence by 5%, while a delay of 12 months would reduce the prevalence by 10%. One approach to achieving a delay in the onset of AD is to investigate lifestyle interventions that could be widely implemented with a favorable risk-benefit relationship and socioeconomic profile. Amongst such interventions, there is increasing evidence to support the use of ketogenic interventions in AD. Indeed, it is well known that cerebral glucose metabolism is impaired in AD, even at a preclinical stage, and a growing body of literature suggests that these findings may represent a primary pathogenic mechanism leading to neurodegeneration. Ketones are readily taken up by the brain and can serve as an alternative energy source for neurons and glia, hypothetically bypassing the glucose uptake deficit in AD. In this invited review we discuss the preclinical as well as clinical work aiming to increase ketones as a primary intervention in AD, including variations of the ketogenic diet, medium chain triglyceride supplementation, and newer, more experimental approaches.
Brain Stimulation in Alzheimer’s Disease Trials
Authors: Benussi Alberto , Borroni Barbara
Published: December 2024

Alzheimer’s disease (AD) continues to lack definitive curative therapies, necessitating an urgent exploration of innovative approaches. This review provides a comprehensive analysis of recent clinical trials focusing on invasive and non-invasive brain stimulation techniques as potential interventions for AD. Deep brain stimulation (DBS), repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and transcranial alternating current stimulation (tACS) are evaluated for their therapeutic efficacy, safety, and applicability. DBS, though invasive, has shown promising results in mitigating cognitive decline, but concerns over surgical risks and long-term effects persist. On the other hand, non-invasive methods like rTMS, tDCS, and tACS have demonstrated potential in enhancing cognitive performance and delaying disease progression, with minimal side effects, but with varied consistency. The evidence hints towards an individualized, patient-centric approach to brain stimulation, considering factors such as disease stage, genetic traits, and stimulation parameters. The review also highlights emerging technologies and potential future directions, emphasizing the need for larger, multi-center trials to confirm preliminary findings and establish robust clinical guidelines. In conclusion, while brain stimulation techniques present a promising avenue in AD therapy, further research is imperative for more comprehensive understanding and successful clinical implementation. Through this review, we aim to catalyze the scientific discourse and stimulate further investigation into these novel interventions for AD.
Functional Magnetic Resonance Imaging in Alzheimer’s Disease Drug Trials: A Mini-Review
Authors: Alghamdi Mohammed , Braidy Nady
Published: December 2024

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative pathology that leads to cognitive decline and dementia, particularly in older adults. It disrupts brain structure and function, with neurotoxic amyloid-β (Aβ) plaques being a primary pathological hallmark. Pharmacotherapeutic trials targeting Aβ and other AD pathological features aim to slow disease progression. Functional magnetic resonance imaging (fMRI) is a non-invasive tool that visualizes brain functional activity, aiding in evaluating the efficacy of AD drugs in clinical trials. Objective: This mini-review explores the role of fMRI in evaluating the impact of AD pharmacotherapeutic clinical trials conducted in the past seven years. Methods: Literature was systematically searched using two databases. The risk of bias was assessed with the Revised Cochrane risk-of-bias tool (RoB-2) for randomized clinical trials (RCTs). Results: Four studies using fMRI to investigate AD drug efficacy were included. Cholinesterase, glutamatergic, and sero- tonergic drugs showed significant positive effects on brain functional activity, especially within the default mode network. Functional connectivity (FC) changes due to drug intake were linked to cerebellar and cholinergic decline in AD, correlating with improved global cognition and fMRI task performance. Conclusions: Recent RCTs demonstrate fMRI’s ability to reveal longitudinal FC pattern changes in response to AD drug treat- ments across disease stages. Positive FC changes in distinct brain regions suggest potential compensatory mechanisms from drug intake. However, these drugs have limited efficacy, necessitating further research to enhance specific pharmacological interventions for clinical application.
Design and Production Technology of the Main Hydrofoil of the Moth-Class Sailboat
Authors: Ljubenkov Boris , Fržop Duje , Galić Luka , Dević Matej
Published: December 2024

The Moth-class sailboat belongs to the international class of sailboats. It is the fastest single-seater class in the world. A vessel that wants to compete in the Moth class must have a certificate from an International Organization that defines the rules and dimensions of the entire sailboat, which limits design. The equipment of the sailboat includes two hydrofoils – main and stern. Hydrofoils must be defined in accordance with the rules. The paper presents the principle of selection of elements of the main hydrofoil assembly, which includes the foil profile, holder and mechanical angle of incidence regulator. Asymmetric and symmetric foil profiles and hydrofoil holders were considered, which were analyzed with software packages. For the selected foil profile and main hydrofoil holder, the choice of materials, laminate plan and production technology are shown. In conclusion, the advantages and disadvantages of the chosen solutions are commented.
Technology Evaluation of Augmented and Mixed Reality Systems in Shipbuilding Processes: Preliminary Report
Authors: Mimica Ratko , Željković Ivana , Settler Vincent , Köster Nina , Gąsiorek Adam , Neufeld Michal
Published: December 2024

This preliminary report will present the latest results of a demonstration level testing of augmented (AR) and mixed reality (MR) devices in shipbuilding processes as a part of the Mari4_YARD project. The main goal of these tests and the project is to develop human-centric solutions which can preserve industry-specific knowledge, enhance the possibilities of presented technologies and improve work tasks’ performance. The tests will also help to define what kind of performance level indicators can be measured in the shipyard’s digital and real environment and can they be achieved.
HISTORIA EST MAGISTRA VITAE. The Hvar Naval Arsenal – Building, Repair and Maintenance of Patrol Ships of East Adriatic Communes Under Venice
Authors: Lokošek Nives , Štefić Florian
Published: December 2024

At the time of the First World Maritime Revolution around 1300, the Venetian General Commandment of the Sea reorganized its navy in 1330; its war ships operated from Corfu to Levant and on the Levant, while the Venetian Adriatic Fleet stationed for centuries on the island of Hvar. The city of Hvar was developing under the Venetian rule (1420–1797) as a naval arsenal for building (in times of conjucture), repair and maintenance of the patrol galleys of the eastern Adriatic towns-communes under Venice. It was a fast and efficient replacement of ships on the slipways, as well as quality building and maintenance of serial ships on the ground floor of a monumental arsenal building. The naval arsenal in Hvar, due to its favorable geographical location was the extended arm of the Great arsenal of Venice, and thanks to this fact, the Hvar arsenal transmitted new and developed its own know-how and experience, and technologically, socially and economically influenced the development of the city of Hvar, middle Dalmatia and especially of Adriatic shipbuilding, although in the circumstances of a rigid governance of the Venetian oligarchy, to the interests and profits of which all was subordinated and strictly supervised.
Afferents to Visually Responsive Grafts of Embryonic Occipital	Neocortex Tissue Implanted into V1 (Oc1) Cortical Area of Adult Rats
Authors: Gaillard Frederic , Girman Sergej V. , Gaillard Afsaneh
Published: December 2024

The aim of this study is to determine, as precisely as possible, the topography and the density of host afferents to visually responsive grafts of occipital embryonic cells implanted in block form into the occipital neocortex of adult rats. The presence of visual activity in the grafts was assessed through field potential and single unit electrophysiological recordings. Field potentials appeared triphasic in shape, had low peak-to-peak amplitude (= 100 μV), and had normal time latencies (~30 msec). Polarity reversal was never observed. Single unit recordings showed that graft neurons exhibited normal (desynchronized) spontaneous activity, had discrete receptive fields (~20° in dia.), and responded to small stationary light flashes. A topic projection of the visual field in the grafts was also observed. Injections of cholera toxin sabunit B (CTB) into these responsive grafts induced retrograde labeling in almost all the brain regions normally projecting to the occipital cortical areas. The visual related cortical (Oc 1, Oc2) and thalamic (LP, LD, LGB) regions of the host provide the largest contingent (70-75%) of afferents to the graft. Finally, one of the major findings of this study is that 93-97% of the labeled cortical cells were found in cortical layers V and VI with a net preference for layer VI. A noticeable proportion of these layer VI labeled neurons (15-20%) was systematically observed in sublayer VIb, very close to, or even within, the white matter. We suggest thus that grafts inserted into the occipital cortex of adult rats receive functional visual inputs through various neuronal circuits. Visual inputs could be conveyed to graft eells by: (i) regenerating axons of geniculate neurons previously innervating the injured cortical site; (ii) formation of collateral branches from thalamic axons ending normally in the host cortex close to the graft boundary; and (iii) development of neuronal processes from cells located in the host cortex, mainly in layers V and VI of the occipital areas. Depending on multiple factors, yet unknown but very likely related to the host-graft integration, the cortical circuits might be either the principal afferent inflow to the graft or only a complement to the thalamic input.
Evidence of Increased Oxidative Stress in Hippocampal Primary	Cultures of Trisomy 16 Mouse
Authors: Hanbauer Ingeborg , Galdzicki Zygmunt , Rapoport Stanley I. , Scortegagna Marzia
Published: December 2024

In the trisomy 16 mouse the increased gene dosage of SOD-1 increases H2O2 production that results in increased oxidative stress. We report here that in hippocampal primary cultures, metallothionein (MT)-I/II immunoreactivity was present mainly in glial fibrillary acidic protein-immunolabeled cells. Western blot analysis showed a two-fold higher level of MT-I/II in trisomy 16 mice then in euploid littermates. In contrast, the immunoreactivity of glutamine synthetase, another glia-expressed protein, was similar in hippocampal cultures of trisomy 16 mouse and euploid littermates. Oxyblot analysis of hippocampal cultures showed that the carbonyl content in several protein bands was higher in trisomy 16 mice than in euploid littermates giving evidence for increased oxidative stress in trisomy 16 mouse cultures. To evaluate the responsiveness of MT-I/II to agents that increase the level of reactive oxygen species in cells we measured the effect of H2O2, kainic acid, (±) ACPD, and B-amyloid peptide 1-42. Western blot analysis documented that in hippocampal cultures of euploid littermates MT-I/II was maximally increased by 50 µM H2O2, 100 µM kainic acid, 10 µM (±)ACPD, or 1.0 mM B-amyloid peptide 1-42, whereas in those of trisomy 16 mice no furter increase above the elevated level was observed. Our data suggest that in the trisomy 16 mouse the production of reactive oxygen species may have shifted the intracellular redox environment that could have alerted the susceptibility of MT-I/II transcription. The possibilty that transcription factors whose activation may be essential to initiate MT-I/II transcription get oxidized has yet to be examined.