bluuebunny/crossref_metadata_2025 huggingface dataset:
Analisis Biaya Produksi Terhadap Pendapatan Petani
Authors: Yuliana  , Sudiyarto Nining , Rachman Rosyidah , Sutrisno Eko , Rahayu Sri
Published: December 2024

Sektor pertanian dapat memiliki kemampuan untuk menghasilkan surplus, hal ini terjadi bila produktifitas di perbesar sehingga menghasilkan pendapatan petani yang lebih tinggi. Peningkatan taraf hidup tersebut diperoleh dengan peningkatan produk pangan baik melalui intensifikasi, ekstensifikasi dan deversifikasi pertanian yang diharapkan dapat memperbaiki taraf hidup petani, memperluas lapangan pekerjaan bagi golongan masyarakat yang masih tergantung pada sektor pertanian. Tujuan penelitian ini adalah untuk menganalisis biaya produksi terhadap pendapatan petani padi di dusun Bagetango Kecamatan Lopok, Sumbawa. Metode penelitian kuantitatif digunakan dalam penelitian ini, melalui uji regresi linier berganda, biaya produksi dalam penelitian ini diantaranya adalah luas lahan, bibit, pupuk, pestisida,  dan tenaga kerja, dengan bantuan Statistical Package for the Social Sciences (SPSS), berdasarkan tujuan yang ingin dicapai, maka penelitian ini menggunakan pendapatan petani padi di Dusun Bagetango, dapat dicapai dengan produksi rata-rata setiap responden selanjutnya dikali dengan harga jual produksi sehingga diperoleh pendapatan total. Hasil penelitian menunjukkan bahwa Pengaruh biaya produksi terhadap pendapatan petani sangatlah signifikan. Jika biaya produksi terlalu tinggi tanpa diimbangi dengan hasil yang memadai atau harga yang baik, pendapatan petani akan menurun. Oleh karena itu, untuk meningkatkan pendapatan, petani perlu mengelola biaya produksi dengan bijak, memanfaatkan teknologi, dan memonitor perubahan harga pasar.
Pengaruh Dimensi Corporate entrepreneurship dan Performa Firma: Sebuah Studi Kualitatif
Authors: Kirana Indah Pramesthi , Purnomo Margo , Purbasari Ratih
Published: December 2024

Corporate entrepreneurship merupakan kegiatan entrepreneur yang dilakukan oleh firma yang sudah cukup lama berdiri dan stabil yang memungkinkan mereka untuk mengikuti dinamika pasar dengan mendorong kemampuan inovasi dan menciptakan bisnis baru dalam perusahaan. Meskipun menarik dan penting, tidak banyak perusahaan yang menyadari pentingnya memiliki pola pikir entrepreneurial pada perusahaan yang mampu membantu bisnis terus berkelanjutan. Penelitian ini dilakukan dengan tujuan membuktikan bagaimana Corporate entrepreneurship dan dimensinya mampu membentuk reputasi perusahaan dan membuatnya tumbuh untuk jangka Panjang. Penelitian menggunakan metode systematic literature review (SLR) dari artikel jurnal bereputasi pada basis data SCOPUS untuk membuktikan keefektifan dari dimensi Corporate entrepreneurship terhadap performa firma. Dari penelitian ini, kami menemukan bahwa Corporate entrepreneurship mampu mempengaruhi firma perusahaan terutama performa keuangan. Dimensi yang ada akan menciptakan pola pikir proaktif yang juga diharapkan akan menjadi pemantik untuk penelitian yang akan dating dan berfokus pada dimensi Corporate entrepreneurship dengan sektor yang lebih beragam dan cakupan negara yang lebih luas.
Sudden blurring of vision and micropsia following acute hot pepper consumption: A case report
Authors: Rastmanesh Reza , Celep Gulcin , Marotta Francesco , Aperio Cristiana , He Fang
Published: December 2024

Background: Retinal hemorrhages are typically considered a major ocular diagnostic sign of underlying systemic vascular disorder. Capsaicin is a bioactive component of chili peppers used in most countries. Capsaicin crosses the blood–brain barrier in an efficient manner. Exposure to dietary capsaicinoids is frequent and often considerable. The presumed lack of capsaicin toxicity in the diet does not rule out the possibility of rare adverse effects on the central nervous system, particularly the retina, as outlined in this report. 
Objective: The purpose of this case report is to describe the ocular issues occurring to a man who developed retinal hemorrhage following overconsumption of hot chili. 
Methods: A case of a 34-year-old man, who reported sudden blurring of vision and micropsia in his left eye following ingestion of a considerable amount of red pepper. 
Results: The case study suggests that acute or chronic consumption of substantial amounts of hot red pepper in individuals with high reactivity towards TRPV1 agonists and/or higher expression of TRPV1 receptors in retinal ganglion cells causes retinal neovascularization. 
Conclusion: Acute consumption of large amounts of red pepper in susceptible individuals may harm vision.
Keywords: Capsaicin; Red Chili; Retinal hemorrhage; Optometry; Micropsia
Vstop slovenskega izdelka na hrvaški trg: primer izdelka Hair Food Oil Elixir
Authors: Černčič Ana , Čeru Petra Viki , Frece Tajda , Vukasović Tina
Published: December 2024

V članku proučujemo širitev izdelka Hair food Oil Elixir slovenskega podjetja Méra Collection na hrvaški trg. Slovensko podjetje Méra Collection je predstavilo svoj izdelek Hair Food Oil Elixir, ki je bil takoj po izidu novembra 2021 velik prodajni uspeh. Izdelek je prejel tudi prestižni naziv najboljšega izdelka za nego las s strani revije Cosmopolitan. Gre za inovativen izdelek, sestavljen iz petih posebej izbranih olj za lase, ki zagotavljajo hranljivo nego in prijeten vonj. Uporabniki so izrazili izjemno zadovoljstvo z izdelkom, ki je primeren tako za globinski tretma kot za vsakodnevno uporabo, hkrati pa ščiti lase pred klorirano vodo in soljo. Strategija vstopa na hrvaški trg se osredotoča na posredni izvoz, kjer je v proces mednarodne menjave vključen domači posrednik. To omogoča podjetju nižje ravni tveganj, stroškov in ohranjanje obstoječe marketinške strategije. Kljub temu pa prinaša tudi nekatere izzive, kot so dodatni stroški in pomanjkanje nadzora nad marketinškim spletom.
Pri prilagajanju izdelka za hrvaški trg je ključna lokalizacija embalaže in informacij o izdelku v hrvaškem jeziku. Distribucija se osredotoča na glavna distribucijska središča, kot je Zagreb, s poudarkom na spletni prodaji. Promocijske aktivnosti so usmerjene v večja nakupovalna središča, splet in družbena omrežja, pri čemer bo sodelovanje z lokalnimi vplivneži in mediji igralo ključno vlogo.
Driving sustainability in Indonesia: the importance of corporate citizenship in realizing sustainable development goals
Authors: Hakim Arif Rahman , Asfiah Nurul
Published: December 2024

Purpose of the article – Corporate Citizenship (CC) and Sustainable Development Goals (SDGs) are two interrelated and essential concepts to achieve sustainable development by 2030. This topic is particularly interesting and relevant today, where companies are expected to pursue profits and contribute to social and environmental well-being. This study aims to describe the implementation practices of corporate citizenship in supporting the achievement of the Sustainability Development Goals of companies in Indonesia.
Research methodology – The research method used is a literature review of journals/articles relevant to the topic.
Findings – This study emphasizes the significance of adopting corporate citizenship to aid in accomplishing Indonesia's Sustainable Development Goals. Corporate citizenship significantly impacts employees, business performance, and sustainability.
Practical implications – The study recommends incorporating CC principles into business strategies and working with stakeholders to speed up the achievement of the SDGs, bolstered by government policies that endorse CC practices. Companies in Indonesia need to participate in CC to achieve the SDGs and create a more sustainable future.
Originality/Value – Exemplary CC implementation has been proven to help various SDGs goals, such as poverty alleviation, improving the quality of education, health, welfare, and action on climate change. The company views the CC program as a strategic investment that positively affects society and the environment while offering benefits like enhanced business performance and improved reputation.
The importance of product innovation in maintaining a competitive advantage
Authors: Sarkar Ahmed  Saeed , Hazhar Omer Mohammed , Rawa Amjad Muhamed , Rezhwan Fayaq Othman
Published: December 2024

Product innovation is crucial in creating and sustaining a competitive advantage for companies. Companies can differentiate themselves from competitors by constantly improving, introducing new products, and appealing to customers. The success of product innovation depends not only on how new the product is but also on its quality and Price. Therefore, the relationship between product innovation, Price, and quality is vital for creating and maintaining a competitive advantage. This study analyzes the relationship between product innovation and (price, quality) with a sustainable competitive advantage, the data shows that there is an effective and positive relationship between product innovation and price, quality. Additionally, we collected data through forum questionnaires and analyzed it using the multiple regression method, and We used SPSS version 25 for assistance in data analysis. So, the study can analyze the influence of the independent variables (product innovation) on the dependent variable (sustained competitive advantage). After analyzing the data, it was found that process innovation, product innovation, Price and quality positively impact sustained competitive advantage. The results also indicate that these three independent variables significantly affect the dependent variable.
Types of scientific leadership (on the example of Russian linguistics)
Authors:   Institute of Linguistics, Russian Academy of Sciences, Alpatov Vladimir M.
Published: December 2024

Research teams are of a different nature. They can be informal, yet they can acquire official status promptly or after a while (institute, sec-tor, department, etc.). In any case, the team needs a scientific leader, and if it possesses a formal status, it will acquire an administrative leader as well. Two leaders can coexist in one person, yet this is not always the case. The ar-ticle examines different types of scientific and scientific-organizational leadership using the example of linguistics. The first type is a total leader; an example is the academician N.Ya. Marr. A person like him could only be such a leader; he did not distinguish between the scientific and administrative aspects of his ac-tivities, and under his global ideas, he strove to create entire institutions. Along with it, the institutionalization of the team is possible, under which the scientific leader receives administrative functions. Still, the two types of leaders are often different people. Those who are strong in science do not always know how to lead, while skillful leaders may not be sources of scientific ideas. The scientific leader of the Moscow Dialectological Commission was N.N. Durnovo, and D.N. Ushakov was its admin-istrative leader; V.N. Sidorov remained the scientific leader of the Moscow phonological school, after it gathered at one department, while R.I. Avanesov was the administrative leader.
Attitude to the image of Alexander Nevsky among students–non-historians (on the example of Privolzhsky Research Medical University)
Authors:   National Research University Higher School of Economics, Agarin Efim V. , Khusyanov Timur M. ,   National Research University Higher School of Economics
Published: December 2024

The article presents the results of a sociologi-cal study, which considers the first-year stu-dents’ perception of some historical personal-ities and events. The attitude towards Prince Alexander Nevsky and his policy is in the fo-cus. The study shows that Alexander Nevsky is one of the most significant figures in Russian history, yet his personality is poorly known in details. This statement may be proved by the respondents’ perception that represents all his achievements coming down to two victo-ries – Battle of the Neva against Swedes with the allies (1240) and Battle on the Ice against Livonian Order (1242). The correlation analysis of respondents’ perception demonstrates the relationship between Alexander Nevsky and other historical personalities. This is how the connection in the minds of the respondents can be traced between the medieval prince and the figures of I.V. Stalin and G.K. Zhukov, as well as the Great Patriotic War. In this case, Alexander Nevsky is related not so much to his own victories as to that recent time, when his image gave hope to the Soviet people.
Internet meme as a way of representing reality: between dystopia and myth
Authors:   Saratov State University, Artamonov Denis S.
Published: December 2024

The article considers the phenomenon of In-ternet memes in the context of the mytholo-gization of ideas about reality. The author fo-cuses on Internet memes of dystopian con-tent and speaks about dystopia as an object representing the reality surrounding a person. He considers the Internet meme as a commu-nication phenomenon of digital culture. The Internet meme has a complex structure and reflects the views of Internet users on the agenda, their worldview, social and political system of society. In the article, the author contrasts the understanding of the meme within the framework of evolutionary biology and the theory of mind, which was developed within the framework of the so-called memet-ic approach, with the definition of a meme as a media meme and an Internet meme. The author supports the theory of media and communication interpretation of the Internet meme, and traces the connection between the metaphor and the myth presented in it. The metaphorical nature of the Internet meme explains its mythological nature. Meta-phorical constructions serve as a way to en-code myths in Internet memes, as a result of which they mythologize the message con-tained in them. The inclusion of dystopian im-ages of mass culture in Internet memes inevi-tably leads to their mythologization. The theme of dystopias appears in Internet memes as a reaction to the negative aspects of everyday reality, or as an expression of us-ers' attitude to the genre as a whole or specif-ic works, which indicates the popularity of dystopian images among users. Through them, Internet users express their critical attitude to reality in visual-text digital format commu-nication messages.
About uselessness and usefulness of the meme’s short life
Authors:   South Ural State University (National Research University), Emchenko Evgeniya P.
Published: December 2024

In their paper, the authors develop an idea of the original publication, according to which the meme is not the simplest atomic unit of culture – it is more complex than it seems at first glance. In this regard, the article by A.A. Dydrov points out a few most expressive characteristics of the meme, such as the critical charge and the ability to reassemble the referent in its interpretation. The authors give their reflections on this paper, where the meme is considered as an innovative type of representation in comparison with the classical ones in the space of new media communications. In the criticism of the meme, there is a significant and in-demand work in the information age on compacting and reformatting the configuration of the chosen referent for its “new life” in the labyrinths of the Internet. At the same time, the critical charge is created at the cost of eliminating the ontological volume and multidimensionality of the referent, thereby becoming local, pointwise directed, understandable without additional reflections and therefore effective in postmodern cultural spaces. Considering the media effect of the meme, the authors complement the complex of its characteristics with “semiotic omnivore” and “muesli effect”. In addition, as part of the appeal to the meme trend, the relevance of the consideration of ecomemetics is indicated in the article.
Proof for the existence of God: Unfulfilled project of the union between faith and reason
Authors:   National  Research Lobachevsky State University of Nizhni Novgorod, Volkov Yuri K.
Published: December 2024

Proceeding from the assumption of the pos-sible union between the sphere of rational – mainly philosophical and theological – and the sphere of irrational – the proper religious comprehension of transcendent entities, the article considers the main options for proving the existence of God. The author formulates the purpose and objectives of the study and chooses a comparative research method cor-responding to them based on such an accen-tuated consideration of the problem of prov-ing the existence of God. The study results in the following conclusions. 1. There are two levels of proof of the existence of God: the level of rational-theoretical knowledge and the level of religious-practical revelation within which relations of combination and exclusion can arise. 2. The cultural and histor-ical prerequisites that determined the ideo-logical split between ancient philosophy and Christian faith, yet preserved their continui-ty, include the consequences of the trans-formation of rationalism into a kind of reli-gion. 3. There are two main proofs of the ex-istence of God – ontological and cosmologi-cal. In addition, the physic-theological (teleo-logical) argument of cosmological proof exists and is widely used. 4. The considered proofs of the existence of God confirm the validity of the conclusion that it is impossible to ra-tionally prove or refute their original thesis without taking into account the irrational features of religious truth. The final section of the article considers a phenomenological version of the proof of the existence of God as its kind of epilogue. The general conclu-sion of the study is as follows. Although the proof of the existence of God has not lost its ideological relevance over the long history of its existence it yet cannot be attributed to the category of implemented projects of the union between faith and reason.
Covid-19 in the context of the Russia’s citizens’ everyday life. Some conclu-sions of the focus group discussions
Authors:   Institute of Sociology of FCTAS RAS, Barash Raisa E.
Published: December 2024

Applying to the sociological data from the focus group research, conducted in three Russia’s regions (in Republic of Bashkortostan, in Vologda Region and in Moscow city), the author examines the impact of the COVID-19 on the emotional condition of the Russia’s citizens and their perception of the current situation in the state, as well as on the social consolidation during 2019-2021 and on their attitude towards digital communication. The author summarizes that the pandemic has highlighted the low level of interpersonal trust and consolidation in Russia’s society and even increased disunity and confirmed that citizens used to care mostly about their inner circle of family, friends and some like-minded people. Despite the intensive use of social media during the pandemic, digital communication in Russia today is demanded mainly by young people who fundamentally avoid television content. Applying regularly to the news and analytical content of the Internet media, Russia’s youth, however, treats any information with great caution and distrust, whether it is received from both digital and traditional media.
Culture and human potential of Russia: challenges of civilizational development in the XXI century
Authors:   Institute of Philosophy, Russian Academy of Sciences, Veryaskina Valentina P.
Published: December 2024

The relevance of the problem is related to the need for a theoretical understanding of the challenges to human development in connection with the transition to post-industrial development and the knowledge economy, with the introduction of new tech-nologies and with Russia’s search for a path to the future. In these conditions, the transfor-mation of a person inevitably takes place. It is expressed in personal modernization associat-ed with the interaction with the social insti-tutions of modernity, among which capitalism is dominant. The paper shows that the trans-formation of a person of new modernity (turn of the 20th–21st centuries) is associated with a change in the nature of labor and with the demand for a new type of worker, whose po-tential is focused on creativity, innovation and the development of human capital. It is noted that the impact of the latest technologies (digital and biotechnologies) has ambivalent trends. With the growing demand for special-ists of a high level human capital in the field of knowledge (cognitariat), the replacement of labor with technologies leads to the emergence of a precariat and to a change in the middle class status. These processes affecting human potential are taking place in the con-text of growing inequality around the world. The author comes to the conclusion that in the world, under the influence of the latest technologies and geopolitical processes, a tendency to disciplinary capitalism is forming. The freedom space of human development is narrowing, and discipline, supervision and manipulation of human consciousness with the help of technology are intensifying. At the same time, social inequality is a catalyst for limiting opportunities for human development. The emergence of problems in the Rus-sian civilizational development requires economic and political measures to stop negative trends. Such measures should be adequate to the challenges and rely on the national culture, the mentality of Russians, the social state and sovereignty.
Objectivity: a regulative ideal, or an imaginary goal?
Authors:   Institute of Philosophy, Russian Academy of Sciences, Sokolova Tatiana D.
Published: December 2024

The article is a response to Alexandra Argama-kova’s reflections on the role of objectivity for research in the field of social epistemology. In our reasoning, we start from the definitions of objectivity given in the logical dictionary and philosophical encyclopedia, and identify theo-retical difficulties associated with an essential-ist definition of the concept of objectivity. From the point of social epistemology view, the most promising way to approach objectivi-ty is to define it as a set of scientific practices. However, the lack of consensus on the under-standing of how exactly objectivity should be defined makes it impossible to raise the ques-tion of distinguishing between subjective and objective elements in cognitive practices: sub-jective factors can be considered as objective components of scientific research, while the objectivity of scientific practices can be deconstructed and relativized, that is, can be reduced to the subjective
Scientific revolutions without incommensurability
Authors:   Institute of Philosophy, Russian Academy of Sciences, Argamakova Alexandra A.
Published: December 2024

Thomas Kuhn’s viewpoint tells that scientific revolutions and the new paradigms cannot be understood without incommensurability. It me-ans radical conceptual novations and disruption with the previous tradition of thinking. However, incommensurability does not possess the only shared treatment. Be-sides its status as a neces-sary attribute of sci-entific revolutions is not firmly supported. Philosophy of Kuhn inspired social studies of scientific cognition, which bloomed in post-positivism, sociology of knowledge, STS and social epistemology. He not only laid the foundations for scientific revolution theory, but also developed sociology of science justi-fying formation mechanisms for scientific be-liefs. For Kuhn, scientific revolutions are an objective phase in know-ledge history, when creative development begins and the subse-quent paradigm emerges. The author rejects objectivity of scientific revolutions in the Kuhnian sense and strengths their social in-terpretation, which explains the proliferation of criteria in evaluation of scientific discover-ies. Scientific revolutions not only describe the logic and history of scientific thinking, but actually they prescribe imperatives and prin-ciples for science organization. In such a sense, they function as a pragmatic idea, a signal superstructure over cognitive practice, allowing to distribute recognition, attention, respect and other assets among actors en-gaged in cognition and intellectual work. The final part of the article clears up what kind of goals can be pursued by discourse over scien-tific revolutions.
Varoglutamstat: Inhibiting Glutaminyl Cyclase as a Novel Target of Therapy in Early Alzheimer’s Disease
Authors: Feldman Howard H. ,   the ADCS VIVA-MIND Study Group, Messer Karen , Qiu Yuqi , Sabbagh Marwan , Galasko Douglas , Turner R. Scott , Lopez Oscar , Smith Amanda , Durant January , Lupo Jody-Lynn , Revta Carolyn , Balasubramanian Archana , Kuehn-Wache Kerstin , Wassmann Tanja , Schell-Mader Sylvia , Jacobs Diane M. , Salmon David P. , Léger Gabriel , DeMarco Mari L. , Weber Frank
Published: December 2024

Background: Varoglutamstat is a first-in-class, small molecule being investigated as a treatment for early Alzheimer’s disease (AD). It is an inhibitor of glutaminyl cyclase (QC), the enzyme that post-translationally modifies amyloid-β (Aβ) peptides into a toxic form of pyroglutamate Aβ (pGlu-Aβ) and iso-QC which post-translationally modifies cytokine monocyte chemoattractant protein-1 (CCL2) into neuroinflammatory pGlu-CCL2. Early phase clinical trials identified dose margins for safety and tolerability of varoglutamstat and biomarker data supporting its potential for clinical efficacy in early AD. Objective: Present the scientific rationale of varoglutamstat in the treatment of early AD and the methodology of the VIVA-MIND (NCT03919162) trial, which uses a seamless phase 2A-2B design. Our review also includes other pharmacologic approaches to pGlu-Aβ. Methods: Phase 2A of the VIVA-MIND trial will determine the highest dose of varoglutamstat that is safe and well tolerated with sufficient plasma exposure and a calculated target occupancy. Continuous safety evaluation using a pre-defined safety stopping boundary will help determine the highest tolerated dose that will carry forward into phase 2B. An interim futility analysis of cognitive function and electroencephalogram changes will be conducted to inform the decision of whether to proceed with phase 2B. Phase 2B will assess the efficacy and longer-term safety of the optimal selected phase 2A dose through 72 weeks of treatment. Conclusions: Varoglutamstat provides a unique dual mechanism of action addressing multiple pathogenic contributors to the disease cascade. VIVA-MIND provides a novel and efficient trial design to establish its optimal dosing, safety, tolerability, and efficacy in early AD.
Leucettinib-21, a DYRK1A Kinase Inhibitor as Clinical Drug Candidate for Alzheimer’s Disease and Down Syndrome
Authors: Meijer Laurent , Chrétien Emilie , Ravel Denis
Published: December 2024

Alzheimer’s disease (AD) and Down syndrome (DS) share a common therapeutic target, the dual-specificity, tyrosine phosphorylation activated kinase 1A (DYRK1A). Abnormally active DYRK1A is responsible for cognitive disorders (memory, learning, spatial localization) observed in both conditions. In DS, DYRK1A is overexpressed due to the presence of the DYRK1A gene on chromosome 21. In AD, calcium-activated calpains cleave full-length DYRK1A (FL-DYRK1A) into a more stable and more active, low molecular weight, kinase (LMW-DYRK1A). Genetic and pharmacological experiments carried out with animal models of AD and DS strongly support the idea that pharmacological inhibitors of DYRK1A might be able to correct memory/learning disorders in people with AD and DS. Starting from a marine sponge natural product, Leucettamine B, Perha Pharmaceuticals has optimized, through classical medicinal chemistry, and extensively characterized a small molecule drug candidate, Leucettinib-21. Regulatory preclinical safety studies in rats and minipigs have been completed and formulation of Leucettinib-21 has been optimized as immediate-release tablets. Leucettinib-21 is now undergoing a phase 1 clinical trial (120 participants, including 12 adults with DS and 12 patients with AD). The therapeutic potential of DYRK1A inhibitors in AD and DS is presented.
Alzheimer’s Disease and (Phyto) Estrogen Treatment: Modification of Effects by Age, Type of Treatment, and Duration of Use
Authors: Kuck M.J. , Begde Ahmet , Hawkins Katie , Hogervorst Eef
Published: December 2024

Background: There is a continued debate on whether menopausal hormone therapy (MHT) protects women against Alzheimer’s disease (AD). It is also unclear whether phytoestrogen could be an alternative treatment for AD. Objective: To investigate whether mixed study findings may be due to differences in age at initiation of MHT and duration of prescription of different types of MHT using meta-analyses. Methods: After a systematic literature search, meta-analyses were carried out using Cochrane Revman 5.4.1.software including data from large nationwide studies of registered medically diagnosed AD and prescribed MHT. These analyses were stratified for duration and type of treatment, by age at start of prescription of therapy. Insufficient quality data were available for phytoestrogen treatment and AD meta-analyses. Results: A total of 912,157 women were included from five registries, of whom 278,495 had developed AD during follow-up. Meta-analyses suggested a small increased AD risk after 5–10 years prescription of combination MHT regardless of age, and over 10 years only in women younger than 60 years of age. No association was seen for estrogen alone for women younger than 60 years of age, but AD risk did increase for women over 60 years of age for up to 5 years of MHT prescriptions. Conclusions: Combination MHT should probably be prescribed for less than 5 years after menopause to reduce risk for AD, while estrogen alone should not be prescribed to women over 60. For phytoestrogen, small treatment trials suggested some benefit of tempeh (fermented soy), which should be investigated further.
Hormone Replacement Therapy and Alzheimer’s Disease: Current State of Knowledge and Implications for Clinical Use
Authors: Sayfullaeva Jessica , McLoughlin John , Kwakowsky Andrea
Published: December 2024

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder responsible for over half of dementia cases, with two-thirds being women. Growing evidence from preclinical and clinical studies underscores the significance of sex-specific biological mechanisms in shaping AD risk. While older age is the greatest risk factor for AD, other distinct biological mechanisms increase the risk and progression of AD in women including sex hormones, brain structural differences, genetic background, immunomodulation and vascular disorders. Research indicates a correlation between declining estrogen levels during menopause and an increased risk of developing AD, highlighting a possible link with AD pathogenesis. The neuroprotective effects of estrogen vary with the age of treatment initiation, menopause stage, and type. This review assesses clinical and observational studies conducted in women, examining the influence of estrogen on cognitive function or addressing the ongoing question regarding the potential use of hormone replacement therapy (HRT) as a preventive or therapeutic option for AD. This review covers recent literature and discusses the working hypothesis, current use, controversies and challenges regarding HRT in preventing and treating age-related cognitive decline and AD. The available evidence indicates that estrogen plays a significant role in influencing dementia risk, with studies demonstrating both beneficial and detrimental effects of HRT. Recommendations regarding HRT usage should carefully consider the age when the hormonal supplementation is initiated, baseline characteristics such as genotype and cardiovascular health, and treatment duration until this approach can be more thoroughly investigated or progress in the development of alternative treatments can be made.
Treating Alzheimer’s Disease: Focusing on Neurodegenerative Consequences
Authors: Sun Miao-Kun , Alkon Daniel L.
Published: December 2024

Neurodegenerative disorders involve progressive dysfunction and loss of synapses and neurons and brain atrophy, slowly declining memories and cognitive skills, throughout a long process. Alzheimer’s disease (AD), the leading neurodegenerative disorder, suffers from a lack of effective therapeutic drugs. Decades of efforts targeting its pathologic hallmarks, amyloid plaques and neurofibrillary tangles, in clinical trials have produced therapeutics with marginal benefits that lack meaningful clinical improvements in cognition. Delivering meaningful clinical therapeutics to treat or prevent neurodegenerative disorders thus remains a great challenge to scientists and clinicians. Emerging evidence, however, suggests that dysfunction of various synaptogenic signaling pathways participates in the neurodegenerative progression, resulting in deterioration of operation/structure of the synaptic networks involved in cognition. These derailed endogenous signaling pathways and disease processes are potential pharmacological targets for the therapies. Therapeutics with meaningful clinical benefit in cognition may depend on the effectiveness of arresting and reversing the neurodegenerative process through these targets. In essence, promoting neuro-regeneration may represent the only option to recover degenerated synapses and neurons. These potential directions in clinical trials for AD therapeutics with meaningful clinical benefit in cognitive function are summarized and discussed.
Drug Repurposing for Effective Alzheimer’s Disease Medicines: Existing Methods and Novel Pharmacoepidemiological Approaches
Authors: Roberts Jackson A. , Varma Vijay R. , Jones Attila , Thambisetty Madhav
Published: December 2024

Drug repurposing is a methodology used to identify new clinical indications for existing drugs developed for other indications and has been successfully applied in the treatment of numerous conditions. Alzheimer’s disease (AD) may be particularly well-suited to the application of drug repurposing methods given the absence of effective therapies and abundance of multi-omic data that has been generated in AD patients recently that may facilitate discovery of candidate AD drugs. A recent focus of drug repurposing has been in the application of pharmacoepidemiologic approaches to drug evaluation. Here, real-world clinical datasets with large numbers of patients are leveraged to establish observational efficacy of candidate drugs for further evaluation in disease models and clinical trials. In this review, we provide a selected overview of methods for drug repurposing, including signature matching, network analysis, molecular docking, phenotypic screening, semantic network, and pharmacoepidemiological analyses. Numerous methods have also been applied specifically to AD with the aim of nominating novel drug candidates for evaluation. These approaches, however, are prone to numerous limitations and potential biases that we have sought to address in the Drug Repurposing for Effective Alzheimer’s Medicines (DREAM) study, a multi-step framework for selection and validation of potential drug candidates that has demonstrated the promise of STAT3 inhibitors and re-evaluated evidence for other drug candidates, such as phosphodiesterase inhibitors. Taken together, drug repurposing holds significant promise for development of novel AD therapeutics, particularly as the pace of data generation and development of analytical methods continue to accelerate.
Conquering Insulin Network Dysfunctions in Alzheimer’s Disease: Where Are We Today?
Authors: de la Monte Suzanne M.
Published: December 2024

Functional impairments in the brain’s insulin and insulin-like growth factor (IGF) signal transduction networks are recognized mediators of dysregulated energy metabolism, a major driver of the Alzheimer’s disease (AD) neurodegeneration cascade. AD-associated insulin-deficient and insulin-resistant states mimic those of diabetes mellitus and affect all cell types in the brain. Besides accounting for abundant amyloid-β and hyperphosphorylated tau lesions in AD, insulin/IGF pathway dysfunctions cause cortical atrophy, loss of synaptic plasticity, white matter myelin/oligodendrocyte degeneration, astrocyte and microglial neuroinflammation and oxidative stress, deficits in energy metabolism, mitochondrial dysfunction, and microvascular disease. These same neuropathological processes have been linked to cognitive impairment in type 2 diabetes mellitus, Parkinson’s disease, and vascular dementia. Strategies to address metabolic mediators of cognitive impairment have been borrowed from diabetes and other insulin-resistant diseases and leveraged on preclinical AD model data. The repurposing of diabetes drugs led to clinical trials with intranasal insulin, followed by insulin sensitizers including metformin and peroxisome-proliferator-activated receptor agonists, and then incretin mimetics primarily targeting GLP-1 receptors. In addition, other glucose-lowering agents have been tested for their efficacy in preventing cognitive declines. The strengths and limitations of these approaches are discussed. The main conclusion of this review is that we have now arrived at a stage in which it is time to address long-term deficits in trophic factor availability and receptor responsiveness, signaling abnormalities that extend beyond insulin and include IGFs and interconnected pathways, and the need for multi-pronged rather than single-pronged therapeutic targeting to remediate AD and other forms of neurodegeneration.
Incretin Mimetics as Potential Disease Modifying Treatment for Alzheimer’s Disease
Authors: Crook Harry , Edison Paul
Published: December 2024

Alzheimer’s disease is a devastating neurodegenerative condition that exerts a significant global burden. Despite recent efforts, disease modifying therapies remain extremely limited, with a tremendous proportion of patients having to rely on symptomatic treatment only. Epidemiological and pathological overlaps exist between Alzheimer’s disease and diabetes mellitus type 2, with people with diabetes mellitus type 2 at a significantly increased risk of developing Alzheimer’s disease in the future. Incretin mimetics, also known as GLP-1/GIP receptor agonists, are useful tools licensed for the treatment of diabetes mellitus type 2 which have recently been the subject of news coverage for their off-label use as weight loss medications. Emerging evidence highlights the possible neuroprotective function of incretin mimetics in models of Alzheimer’s disease as well as in clinical studies. This review details the pre-clinical and clinical studies that have explored the effectiveness of incretin mimetics to alleviate Alzheimer’s disease associated pathology and cognitive impairment, while also highlighting the progress made to examine the effectiveness of these molecules in Parkinson’s disease. Should clinical trials prove effective, incretin mimetics may be able to be repurposed and become useful novel tools as disease-modifying treatments for Alzheimer’s disease and other neurodegenerative diseases.
Hypercholesterolemia and Alzheimer’s Disease: Unraveling the Connection and Assessing the Efficacy of Lipid-Lowering Therapies
Authors: Pappolla Miguel A. , Refolo Lorenzo , Sambamurti Kumar , Zambon Daniel , Duff Karen
Published: December 2024

This article examines the relationship between cholesterol levels and Alzheimer’s disease (AD), beginning with the early observation that individuals who died from heart attacks often had brain amyloid deposition. Subsequent animal model research proved that high cholesterol could hasten amyloid accumulation. In contrast, cholesterol-lowering treatments appeared to counteract this effect. Human autopsy studies reinforced the cholesterol-AD connection, revealing that higher cholesterol levels during midlife significantly correlated with higher brain amyloid pathology. This effect was especially pronounced in individuals aged 40 to 55. Epidemiological data supported animal research and human tissue observations and suggested that managing cholesterol levels in midlife could reduce the risk of developing AD. We analyze the main observational studies and clinical trials on the efficacy of statins. While observational data often suggest a potential protective effect against AD, clinical trials have not consistently shown benefit. The failure of these trials to demonstrate a clear advantage is partially attributed to multiple factors, including the timing of statin therapy, the type of statin and the appropriate selection of patients for treatment. Many studies failed to target individuals who might benefit most from early intervention, such as high-risk patients like APOE4 carriers. The review addresses how cholesterol is implicated in AD through various biological pathways, the potential preventive role of cholesterol management as suggested by observational studies, and the difficulties encountered in clinical trials, particularly related to statin use. The paper highlights the need to explore alternate therapeutic targets and mechanisms that escape statin intervention.
On the Structural Response of Innovative Plastic Materials for Boatbuilding Applications
Authors: Bertagna Serena , Taucer Marchesi Natasha , Bucci Vittorio , Marino’ Alberto
Published: December 2024

The introduction of innovative materials and the ability to ensure a reduced environmental impact is a topic of significant interest among experts in ship- and boatbuilding sectors. Materials must be able to combine physical and mechanical properties adequate to the intended purpose and uses, while also addressing fundamental aspects of sustainability. As a first aspect, they must ensure recyclability at the end of their lifecycle, combined with low energy consumption and limited exploitation of resources during production. Nowadays, these factors represent key parameters for selecting construction materials, in agreement with the Green Shipbuilding approach. In recent years, innovative plastics able to offer these advantages have been increasingly considered as potential structural materials for small vessels. Indeed, they combine chemical resistance, anti-corrosion properties, and high flexibility while ensuring recyclability possibilities. Given the novelty of adopting such materials for boat construction, it is necessary to investigate their mechanical and strength properties through adequate laboratory testing aimed at characterising maritime applications. The present article, after giving a description of the considered plastic materials in terms of structure and properties, aims to detail a proper experimental campaign for mechanical tests addressed at validating their use for structural purposes in boat constructions.
Towards Cleaner Oceans and Ports: Developing an Eco-Friendly Waste Collecting Vessel
Authors: Karczewski Artur , Reichel Maciej , Pruszko Hanna , Marcinkiewicz Ewa
Published: December 2024

Each year, approximately 8 million tons of plastic waste enter the oceans, making it one of the most pervasive pollution problems globally. This issue has prompted a global call for preventive measures due to its detrimental impact on marine life, fishery resources, coastal livelihoods, tourism, the environment, and long-term human health. Marine debris is a significant environmental concern, affecting both human health and aesthetics. Ports and their surrounding areas face particularly severe challenges due to high waste accumulation and the difficulty of cleanup operations amidst heavy ship traffic. This paper presents the results from the early stage of design for a Waste Collecting Vessel (WCV), a versatile ship capable of performing multiple functions, including surface garbage removal, waste collection from other ships, oil spill recovery, and weed cutting. Our research offers new insights into the design and operation of eco-friendly small ships, contributing to sustainable maritime environmental management. The culmination of this work is a conceptual proposal for a catamaran equipped with advanced technologies for efficient waste management in ports and coastal areas. The design is envisioned to be zero-emission and autonomous.
Feasibility Study on the Potential Using of Ferrocement for Constructing Floats
Authors: Zima Beata , Karczewski Artur
Published: December 2024

In recent years, there has been a significant increase in interest in ferrocement as a material for various engineering constructions. Due to its ease of shaping complex forms, it has been used previously, for example, in constructing ship hulls or tank walls. Apart from the advantages associated with the ability to shape thin elements, improved mechanical properties compared to concrete, and resistance to chemical actions, ferrocement is becoming an increasingly attractive solution for both economic and ecological reasons. The paper presents the results of preliminary analysis aimed at determining the potential use of ferrocement as a material for constructing floats for houseboats. The assumptions regarding the load-bearing structure are presented, and the dimensioning process is described. Due to the lack of standards for the ferrocement structures, the calculations were based on the guidelines of the European standards for concrete and reinforced concrete structures. Subsequently, the focus was on the problems associated with determining the ferrocement strength parameters, as well as discussing the consequences of applying reinforced concrete theory to its calculations. Also, the areas that required reformulation due to the strictly adopted assumptions related to the concrete behavior and the method of load transfer through reinforced sections have been indicated.
D3V-SGD: An Open Source Program for the Design of Ship Grillage Structures
Authors: Prebeg Pero , Kos Gordan , Banjedvorec Dominik , Pavlović Tomislav , Šikić Gordan , Andrić Jerolim
Published: December 2024

Grillage design is one of the most common tasks in ship structural engineering, as many components of a ship’s secondary structures, such as hatch covers and decks, are grillages. This paper presents the current state of development of D3V-SGD, an open-source software tool for the design and analysis of ship grillage structures developed by students and researchers from UNIZAG FSB. Realized as an extension module to D3V, an open-source 3D Modular Viewer in Python, D3V-SGD currently features a parametric model for hatch covers, a GUI with 3D visualization, and automatic generation of analysis models for determining structural responses. These models include both grillage beam analytical methods and FEM using shell elements. For FEM analysis, the open-source program OOFEM has been utilized, recently adopted for the analysis of ship thin-walled structures.