bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Ship Surf-Riding/Broaching Motion Considering the Influence of Wave Drift Force
Authors: Deng Junyi , Chen Siyuan , Zhang Baoji
Published: October 2024

Surf-Riding/Broaching is one of the second generation intact stability failure modes of ships, but due to its strong nonlinearity and uncertainty, there are relatively few researchers. At present, the calculation method for the first and second layer vulnerability criteria of Surf-Riding/Broaching has reached international consensus, while the direct numerical evaluation of Surf-Riding/Broaching is still under research. Direct numerical evaluation is mainly based on the four degree of freedom MMG maneuverability equation to study the motion performance of ships under regular waves. However, in the actual navigation process of ships, the wave drift force will inevitably affect the ship’s motion state, especially the influence of the yaw moment on the ship. On the basis of summarizing previous research results, this article improves the MMG maneuverability equation by adding wave drift force to the wave force term, and studies the ship Surf-Riding/Broaching considering the influence of wave drift force. Taking the ITTC ship A2 fishing vessel as an example, numerical simulations were conducted on its motion state under different influence of initial yaw angle. The research results can provide technical support for the second generation complete stability.
Optimal Selection of Capacitive Sensor Frequency Margin
Authors: Ghemari Zine , Belkhiri Salah
Published: October 2024

To choose the appropriate frequency range, it is necessary to understand the physical behavior of the sensor in different situations. The natural frequency of a capacitive accelerometer is an integral part of its design and material characteristics, and it influences the response of the sensor to various frequencies of vibrational inputs. If the frequency of the vibrating movements is too close to the natural frequency of the accelerometer, this can lead to resonance, which leads to strong oscillations and considerable measurement errors. During our research, we created a comprehensive model to represent the operation of the capacitive accelerometer. This model includes the essential elements that impact sensor performance, such as mass, damping and stiffness, as well as the electrical characteristics of the capacitive sensing mechanism. The study of this model under different conditions made it possible to observe the reaction of the accelerometer to various frequencies of vibration inputs. These simulations allowed us to relate the natural frequency of the accelerometer to the frequency of the vibratory movements. It is essential to take this relationship into account to define the ideal frequency range for the accelerometer. By entering this link, it is possible to choose a frequency range that prevents resonance and reduces measurement errors, improving the accuracy and reliability of the sensor output.
Problem of Multicriteria Optimization of Robots Power Transmission Using Dynamic Similarity Criteria
Authors: Misyurin Sergey Yu. , Nelyubin Andrey P.
Published: October 2024

The problem of choosing the parameters of robot drives using the multicriteria optimization method is considered. At the initial stage, it is proposed to simplify the robotic system by replacing the spatial mechanism that transmits motion with a transfer function (the ratio of the input drive to the end effector speeds) and consider the problem of optimizing the “drive-control” system taking into account the transfer function. This approach greatly simplifies the choice of system parameters without violating the generality of the problem. This approach has a number of advantages, it takes into account the mutual influence of different subsystems on each other and simplifies the general problem of synthesizing the robotic system. The robotic system is studied based on the analysis of differential and algebraic equations (describing the dynamics of the system), moving to a dimensionless model using the similarity theory method. The paper introduces similarity criteria that can be divided into two groups. The first group includes the parameters that characterize the operation of the drive, such as speed, acceleration, inertia, friction forces, and signal processing delay during positioning. The second group includes the parameters of the control: the structural diagram of the control system, gain factors, and the parameters of the transfer function.
An IoT-Controlled Robotic Hand for Hazardous Material Handling
Authors: Varughese Aaron , Vimalraj Rohan , Elango Konguvel , Rajagopal Sivakumar
Published: October 2024

The paper proposes a robotic arm which mimics the action of a real human hand using an Arduino Mega and micro-servo motors can read and record paths in a 3D space. The robotic arm is controlled by an app developed on Blynk IoT that will enable it to move and manipulate objects in the designated area. This apparatus could be used in industries where we require the functions of a human hand but also raises an issue with the safety of the person involved. The industry in focus of this study is the tissue culture industry. Industries in which fragile materials such as tissue subcultures and toxic chemicals are handled could be made safer with the help of a robotic hand to handle the toxic material instead of risking the hand of an actual human being. Another industry in which a robotic arm would be helpful are those which involve heavy lifting or transportation of objects.
Autonomous Perpendicular Parking of a Car-Like Robot in an Unknown Environment
Authors: Gamberov Timur , Eryomin Alexander , Tsoy Tatyana , Martínez-García Edgar Alonso , Magid Evgeni
Published: October 2024

The trend for vehicle automation in the recent decades caused a significant growth of researches in autonomous navigation of robotized cars, obstacle avoidance, and dynamic path planning. This paper presents an algorithm for autonomous perpendicular parking of an Avrora Unior car-like mobile robot. The parking process includes finding a suitable parking space and a perpendicular park maneuver. The proposed solution uses point clustering to accurately determine a parking space. A free space is qualified as a parking plot automatically when the threshold value of the distance between clusters is reached. The parking maneuver involves aligning the robot to the parking slot and moving along an arc-shaped trajectory. The algorithm uses only LiDAR and wheel encoder data to determine the robot’s location relative to parking spaces. The quality of the robot’s parking is estimated by the distance to the boundaries of the parking space. The reliability of the algorithm was successfully validated in Gazebo simulation and in real-world experiments.
Simulation of Traction Power System with Static Var Generator in the Presence of Equalizing Currents
Authors: Komyakov Aleksandr A. , Nikiforov Mikhail M. , Kashtanov Alex L. , Vilgelm Aleksandr S. , Tarasevich Viktor A.
Published: October 2024

The article is devoted to modeling the operating modes of the AC traction power supply system under the conditions of using adjustable reactive power compensation devices (Static Var Generator – SVG). The question of the SVG use effectiveness in the presence of an equalizing current in the traction network is insufficiently studied. The purpose of the study is to evaluate the effect of the equalizing current on the efficiency of the traction power supply system. As an object for research the actual section of the railway was taken. The SimInTech program was chosen as a simulation tool. It has been obtained that the use of the simulations described in the article with a sufficient degree of reliability makes it possible to evaluate the efficiency of the adjustable reactive power compensation devices, including in the presence of an equalizing current. It has been established that the use of SVG under the conditions of an equalizing current can lead to a deterioration in the traction power supply system operating modes. Thus, the electricity losses for the investigated railway section increases by 0.35%, and the uneven loading of traction substations increases from 28.8% to 66.8%. Thus, in the presence of circulating currents, SVG can degrade the energy performance of the traction power supply system.
Experimental Study on Compressive Strength of Polypropylene Fiber-Reinforced Sand
Authors: Liu Yun , Lai Jie , Liu Yuan , Wang Wei
Published: October 2024

In order to conduct in-depth research on the effectiveness of polypropylene fiber-reinforced sand, this paper conducted a compressive mechanical test on the polypropylene fiber-reinforced sand, provided experimental mix proportions, obtained mechanical parameters of reinforced sand with different polypropylene fiber contents, explored the relationship between compressive strength in different polypropylene fiber content, and described the reinforcement effect of polypropylene fiber on sand. In this test, it has been found that when the fiber content exceeds 1%, the overall compressive strength of the improved sandy soil will increase slowly. When the fiber content is greater than 0.5%, the tensile strength of the increased sample decreases. When the content of the curing agent is 15% and the fiber content is 0.5%, the compressive strength compressive strength of polypropylene fiber-reinforced sand can reach 14.1MPa.The research results have a certain driving effect on the application of propylene fibers in civil engineering.
New Progress in Experimental Study of Deep Overburden Characteristics
Authors: Zhang Feiyue , Luo Qixun , Li Xiaoquan , Ma Fulong
Published: October 2024

In recent years, with the further development of water conservancy and hydro-power engineering in our country, more and more water conservancy projects have to be built on the overburden. Great progress has been made in exploration, testing, seepage prevention and deformation calculation of deep overburden at home and abroad. Among them, the exploration and test of deep cover layer of dam foundation is the most basic and main technical problem of using deep cover layer to build dam. The soil test is a direct and effective means to find out the physical and mechanical characteristics of deep overburden, which provides important design and calculation parameters for rational utilization and engineering treatment of deep overburden in river bed. However, the current engineering experience of dam construction on overburden is mostly limited to shallow overburden. With the increase of overburden thickness, how to accurately obtain basic indexes such as natural density, water content and grading have become the focus, difficulty and key point of deep overburden test. The sand layer, clay layer, egg (block) and gravel (broken) layer in the shallow part of the overburden layer can be excavated to obtain the original sample, and then obtain the corresponding basic physical parameters. However, in the survey and design stage, due to the restrictions of survey means and conditions, the basic physical parameters of deep soil can not be obtained by large excavation. Sand layer and clay layer are sampled by conventional drilling, and the density may change. The egg and gravel layers are sampled by conventional drilling, the layers are unchanged, the composition and structure change, and the density is difficult to obtain. This paper introduces the new development of sampling methods for large bore holes, simultaneously, the representative drift-gravel layer of Shuangjiangkou hydropower station is selected, and the relation curve between the laboratory side pressure test modulus and soil layer density is obtained through model test.
Research on the Impact of Hydropower Cascade Development on Regional Transportation Network
Authors: Yu Miao , Li Zhi , Yu Shijia
Published: October 2024

The Party’s two major events have emphasized that transportation is vital to the country’s economy and people’s livelihood. Qinghai Province is rich in water resources and has unique advantages of hydropower and clean energy, and the resource advantages of hydropower ladder development have greatly promoted the development of regional transportation network. In order to clarify the impact of hydropower ladder development on regional transportation network from the theoretical level, this paper visualizes the transportation network of Haidong City in 2014 and 2022 from the perspectives of road network density, connectivity and accessibility. The results show that the inter-regional linkage development pattern is gradually formed in the hydropower gradient development region, and the high road network density area is formed and expanded in the whole region under this pattern, which has the advantage of coordinating the regional development pattern, and the road accessibility of the three southern counties represented by Chuanhua and Hualong is significantly increased, and the transportation network evolution is obvious and the development pattern is stable and rapid.
Evaluation and Improvement Path of Green Operation Level of Large Hydropower Stations from the Perspective of ESG
Authors: Zhang Shaokun , Zhu Jiwei , Yu Miao , Li Zhi
Published: October 2024

The green operation level of large-scale hydropower stations is directly related to the implementation of national energy strategy, protection of ecological environment, and sustainable development of economy and society. To help optimize the green operation performance of large hydropower stations in terms of environmental protection, society, and governance, the AHP-fuzzy comprehensive evaluation method was applied to construct a green operation level evaluation model for large hydropower stations based on the ESG perspective, and the green operation level of G hydropower station was evaluated. The research results are as follows: (1) Based on a comprehensive analysis of the factors affecting the green operation of hydropower stations, a large-scale hydropower station green operation level evaluation index system is established with three dimensions including 18 secondary indicators; (2) Establishing a fuzzy evaluation mathematical model for the green operation level of large-scale hydropower stations using the Analytic Hierarchy Process and fuzzy mathematics theory; (3) The overall result of the green operation level of G hydropower station is “good”, the environmental and social dimension evaluation result is “good”, and the management dimension evaluation result is “average”. This study provides valuable reference and guidance for the green development of large-scale hydropower stations in China, and contributes to the sustainable development of China’s energy industry.
Numerical Study the Effects of N2O Addition on the Combustion Characteristics of Premixed NH3/Air Flames
Authors: Zhang Bo
Published: October 2024

The adoption of NH3 as a fuel for energy generation has garnered significant attention worldwide. Adding N2O is a method that can effectively improve the flammability of NH3, which is of great significance for the practical application of NH3. Hence, this study focuses on providing valuable insights into the combustion characteristics of NH3/N2O/air flames through the chemical kinetic simulation. Results showed that for the NH3/air flames, adding N2O can significantly decrease the ignition delay time and increase the laminar flame speeds, adiabatic flame temperatures, and heat release rates. With the addition of N2O, there are many O free radicals generated due to the decomposition of N2O, which leads to a significant promoting effect of R207: N2O(+M)=N2+O(+M) on flame temperature and LFS. Heat release analysis shows that for N2O-related elementary reactions, R209: N2O+H=N2+OH is the primary exothermic reaction, and R207: N2O(+M)=N2+O(+M) is the primary endothermic reaction. Finally, it is discovered that the addition of N2O will result in an increase in NO emissions, which requires the addition of exhaust gas treatment devices to the burner.
Effect of Gas Velocity on the Transport State of Waste Tyre Particles in a Multi-Chamber Fluidised Bed
Authors: Jia Tianyao , Chen Yekui , Li Chaojie
Published: October 2024

Fluidized bed reactors are commonly used in pyrolysis processes due to their efficient solid-phase mixing. However, waste tire ((WT)) particles can lead to reverse mixing of waste tire particles during fluidization due to the interaction between gas-solid and solid-solid phases, thus affecting the pyrolysis efficiency. In this study, a multichamber fluidized bed is used as the pyrolysis reactor, and the research focuses on adjusting the pyrolysis reaction temperature and the fluidized gas velocity to achieve the simultaneous transformation of the conversion time and the particle residence time of the waste tire particles in the multichamber fluidized bed pyrolysis reactor. The effect of different fluidizing gas velocities on the residence time of particles in the reactor was first evaluated using multiphase flow numerical simulation. Subsequently, cold mode fluidization experiments were conducted and the distribution of semi-coke particles in each pyrolysis chamber at different stages was analyzed using particle image velocimetry (PIV).
Analysis of Hydrodynamic Energy-Saving Device for 85000DWT Bulk Carrier
Authors: Zhuang Yan
Published: October 2024

The 85,000DWT bulk carrier has a relatively large rear section, which is prone to flow separation, resulting in highly uneven inflow fields for the propeller and severe energy loss. To address the problem, three types of hydrodynamic energy-saving devices were designed. With the help of CFD software STAR-CCM+ 20.0, the ship’s hydrostatic resistance and self-propulsion performance were simulated. The rotating motion area of the propeller was specially treated using a multi-reference system model, and the VOF method was used to capture the free surface. The energy-saving effects of three designed energy-saving devices were finally determined at three speeds meeting the design draft. Conclusion drawn after comparison and analysis: the bulk carrier equipped with energy-saving device has energy-saving effects, compared to the one without energy-saving device, with an average energy-saving efficiency of 2.4%; At different speeds, the energy-saving efficiency increases with the speed increasing; At the same speed, comparing the energy-saving effects of three energy-saving devices, the pre-shrouded vanes was determined that it has the best energy-saving effect, with the energy-saving efficiency of 4.48%, followed by the propeller boss cap fins and rudder bulb, with 1.56% and 1.16% respectively.
Application of Cooling Oil in Automotive/Compressor/Metal Processing Fields
Authors: Cheng Liang , Liu Yuxiu , Wang Yonggang , Zhang Jie
Published: October 2024

In industrial production, oil-based coolants (cooling oils) are widely used. The article describes the application of cooling oil in three areas. In the automotive field, it is mainly used for engine cooling. Water-based coolant products are available for conventional engines. However, high-altitude cooling oil is required at high altitudes to solve the problem of water-based coolant evaporation loss and cooling system boiling. In the field of compressors, cooling oil is also called supercoolant, mainly using cooling and lubrication of screw compressors. In metal processing, oil-based cutting fluids (cutting oils) are used in heavy-duty metal cutting and forming surfaces and high-precision products with good lubricity. Oil-based and water-based coolants are complementary in different fields, but there is no uniform regulation for oil-based product standards. It is difficult to determine the appropriate type and quality of oil to use in different industries. This lack of uniformity highlights the need for further research and development in cooling oil standards. The introduction provides some reference for the research (standards) of cooling oil in these three fields.
Analysis of the Impact on Highway Driving Safety by Roadside Slope Photovoltaics and Research on Comprehensive Safety Assurance Measures
Authors: Wang Xu , Zhao Yuan , Bao Xiyong , Wang Xiaoyu
Published: October 2024

In alignment with the developmental objectives of “carbon neutrality” and “carbon peaking,” numerous regions are progressively experimenting with the installation of photovoltaic facilities on highway slopes. However, uncertainties persist regarding the potential impacts on driving safety post-installation, including whether photovoltaic setups may induce glare, interfere with driver navigation, increase the risk of vehicle crossover incidents, or elevate the severity of accidents following collisions with roadside photovoltaic structures. Ensuring the safety of driving subsequent to the installation of photovoltaics on highway slopes is a fundamental prerequisite for such endeavors. Consequently, this study aims to analyze the effects of photovoltaic installations on the slopes of highways on driving safety. It proposes recommendations for suitable road sections for solar installations, establishes technical specifications for photovoltaic facilities, and suggests proactive safety measures and roadside protective requirements to safeguard driving safety in the wake of photovoltaic integration.
State-of-the-Art: Tracing the history, development, and design of integral abutment bridges
Authors: Shedge Hrishikesh N. , Kumar Manoj
Published: October 2024

Integral abutment bridges (IABs) are a family of jointless bridges that have gained popularity owing to their simplified designs and sustainable construction practices. IABs are small- and medium-span bridges that do not have expansion joints or bearings, thereby reducing the cost of maintenance. The span of IABs is primarily dependent on the magnitude of the thermal stresses considered during the design process. However, the adoption of IABs has been limited globally because of the inherent complexity of the design caused by the large number of indeterminacies originating from rigid connections and soil-spile interactions. This has led to variations in the design of IABs among transportation agencies worldwide. This literature review aims to highlight the variations in major IAB projects constructed worldwide. Additionally, the bibliographic analysis performed for IABs identified key topics studied by researchers, which are discussed in detail in the current state-of-the-art. The objective of this literature survey is to provide practical bridge designers and researchers with an understanding of previous and ongoing developments in IABs.
Brain Stimulation in Alzheimer’s Disease Trials
Authors: Benussi Alberto , Borroni Barbara
Published: October 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.
Immunotherapy in Alzheimer’s Disease: Current Status and Future Directions
Authors: Vashisth Kshitij , Sharma Shivani , Ghosh Shampa , Babu M. Arockia , Ghosh Soumya , Iqbal Danish , Kamal Mehnaz , Almutary Abdulmajeed G. , Jha Saurabh Kumar , Ojha Shreesh , Bhaskar Rakesh , Jha Niraj Kumar , Sinha Jitendra Kumar
Published: October 2024

Alzheimer’s disease (AD) is a progressive neurological disorder characterized by memory loss, cognitive decline, and behavioral changes. Immunotherapy aims to harness the immune system to target the underlying pathology of AD and has shown promise as a disease-modifying treatment for AD. By focusing on the underlying disease pathogenesis and encouraging the removal of abnormal protein aggregates in the brain, immunotherapy shows promise as a potential treatment for AD. The development of immunotherapy for AD began with early attempts to use antibodies to target beta-amyloid. The amyloid hypothesis which suggests that the accumulation of beta-amyloid in the brain triggers the pathological cascade that leads to AD has been a driving force behind the development of immunotherapy for AD. However, recent clinical trials of monoclonal antibodies targeting amyloid-β have shown mixed results, highlighting the need for further research into alternative immunotherapy approaches. Additionally, the safety and efficacy of immunotherapy for AD remain an area of active investigation. Some immunotherapeutic approaches have shown promise, while others have been associated with significant side effects, including inflammation of the brain. Sleep has a significant impact on various physiological processes, including the immune system, and has been linked to the pathogenesis of AD. Thus, improving sleep quality and duration may benefit the immune system and potentially enhance the effectiveness of immunotherapeutic approaches for AD. In this review, we discussed the promises of immunotherapy as a disease-modifying treatment for AD as well as possible methods to improve the efficacy and safety of immunotherapy to achieve better therapeutic outcomes.
Stem Cell Interventions in Neurology: From Bench to Bedside
Authors: Pappolla Miguel A. , Wu Ping , Fang Xiang , Poeggeler Burkhard , Sambamurti Kumar , Wisniewski Thomas , Perry George
Published: October 2024

Stem cell therapies are progressively redefining the treatment landscape for a spectrum of neurological and age-related disorders. This review discusses the molecular and functional attributes of stem cells, emphasizing the roles of neural stem cells and mesenchymal stem cells in the context of neurological diseases such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, Parkinson’s disease, and Alzheimer’s disease. The review also explores the potential of stem cells in addressing the aging process. The paper analyzes stem cells’ intrinsic properties of self-renewal, differentiation, and paracrine effects, alongside the importance of laboratory-modified stem cells like induced pluripotent stem cells and transgenic stem cells. Insights into disease-specific stem cell treatments are offered, reviewing both successes and challenges in the field. This includes the translational difficulties from rodent studies to human trials. The review concludes by acknowledging the uncharted territories that warrant further investigation, emphasizing the potential roles of stem cell-derived exosomes and indole-related molecules, and aiming at providing a basic understanding of stem cell therapies.
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: October 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.
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: October 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.
Conquering Insulin Network Dysfunctions in Alzheimer’s Disease: Where Are We Today?
Authors: de la Monte Suzanne M.
Published: October 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.
Ketogenic Approaches for the Treatment of Alzheimer’s Disease
Authors: Gabuzyan Renata , Lee Christopher , Nygaard Haakon B.
Published: October 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.
Amyloid-Directed Antibodies: Past, Present, and Future
Authors: Noorda Keith , Noorda Kevin , Sabbagh Marwan N. , Bertelson John , Singer Jonathan , Decourt Boris
Published: October 2024

Background: Alzheimer’s disease (AD) is the most common neurodegenerative disorder in patient demographics over 65 years old causing debilitating cognitive impairment. Most commonly, AD is diagnosed clinically as “probable AD”, and definitive diagnosis is confirmed through postmortem brain autopsies to detect extracellular amyloid-β (Aβ) plaques and intraneuronal hyperphosphorylated tau tangles. The exact mechanism causing AD is still unknown, but treatments for AD have been actively investigated. Currently, immunotherapies have shown substantial promise in reducing the pathologic and clinical signs of AD. Objective: This review aims to evaluate passive immunotherapies deemed to have promise for further development and use in the treatment of AD. Methods: Immunotherapies were selected via a narrative review of medications that have potential clinical effectiveness with a status of FDA accepted, FDA fast-track, FDA status pending, or emerging therapies poised to pursue FDA approval. Results: This review has yielded two anti-Aβ monoclonal antibodies (mAb) that are currently fully FDA approved, one mAb granted FDA fast-track status, two therapies on hold, three discontinued medications, and three promising emerging therapies. Conclusions: We conclude that, in the near future, passive immunotherapies will be the preferred and evidence-based method of treatment for AD with the presence of brain Aβ deposits for both symptom management and potential slowing of disease progression. Specifically, lecanemab and donanemab will require further clinical studies to optimize patient selection based on safety profiles. Despite some key limitations, these two drugs are paving the way for disease-modifying treatments in patients displaying early signs of amyloid pathology.
PET/CT/MRI in Clinical Trials of Alzheimer’s Disease
Authors: Høilund-Carlsen Poul F. , Alavi Abass , Barrio Jorge R.
Published: October 2024

With the advent of PET imaging in 1976, 2-deoxy-2-[18F]fluoro-D-glucose (FDG)-PET became the preferred method for in vivo investigation of cerebral processes, including regional hypometabolism in Alzheimer’s disease. With the emergence of amyloid-PET tracers, [11C]Pittsburgh Compound-B in 2004 and later [18F]florbetapir, [18F]florbetaben, and [18F]flumetamol, amyloid-PET has replaced FDG-PET in Alzheimer’s disease anti-amyloid clinical trial treatments to ensure “amyloid positivity” as an entry criterion, and to measure treatment-related decline in cerebral amyloid deposits. MRI has been used to rule out other brain diseases and screen for ‘amyloid-related imaging abnormalities’ (ARIAs) of two kinds, ARIA-E and ARIA-H, characterized by edema and micro-hemorrhage, respectively, and, to a lesser extent, to measure changes in cerebral volumes. While early immunotherapy trials of Alzheimer’s disease showed no clinical effects, newer monoclonal antibody trials reported decreases of 27% to 85% in the cerebral amyloid-PET signal, interpreted by the Food and Drug Administration as amyloid removal expected to result in a reduction in clinical decline. However, due to the lack of diagnostic specificity of amyloid-PET tracers, amyloid positivity cannot prevent the inclusion of non-Alzheimer’s patients and even healthy subjects in these clinical trials. Moreover, the “decreasing amyloid accumulation” assessed by amyloid-PET imaging has questionable quantitative value in the presence of treatment-related brain damage (ARIAs). Therefore, future Alzheimer’s clinical trials should disregard amyloid-PET imaging and focus instead on assessment of regional brain function by FDG-PET and MRI monitoring of ARIAs and brain volume loss in all trial patients.
Genistein, A Phytoestrogen, Delays the Transition to Dementia in Prodromal Alzheimer’s Disease Patients
Authors: Viña José , Borrás Consuelo , Mas-Bargues Cristina
Published: October 2024

Alzheimer’s disease is recognized as a complex condition influenced by multiple factors, necessitating a similarly multifaceted approach to treatment. Ideally, interventions should prioritize averting the progression to dementia. Given the chronic nature of the disease, long-term management strategies are required. Within this framework, lifestyle modifications and dietary supplements emerge as appealing options due to their minimal toxicity, limited side effects, and cost-effectiveness. This study presents findings from a double-blind, placebo-controlled bicentric pilot clinical trial, demonstrating the significant cognitive preservation associated with genistein, a phytoestrogen found in soy and various other dietary sources, among individuals with prodromal Alzheimer’s disease. Our prior investigation utilizing APP/PS1 mice elucidated the specific mechanisms through which genistein operates, including anti-amyloid-β, antioxidant, anti-inflammatory, and antiapoptotic effects. These findings underscore the potential of identifying bioactive compounds from dietary sources for the management of Alzheimer’s disease.
Positron Emission Tomography/Computed Tomography Imaging in Therapeutic Clinical Trials in Alzheimer’s Disease: An Overview of the Current State of the Art of Research
Authors: Triumbari Elizabeth Katherine Anna , Chiaravalloti Agostino , Schillaci Orazio , Mercuri Nicola Biagio , Liguori Claudio
Published: October 2024

The integration of positron emission tomography/computed tomography (PET/CT) has revolutionized the landscape of Alzheimer’s disease (AD) research and therapeutic interventions. By combining structural and functional imaging, PET/CT provides a comprehensive understanding of disease pathology and response to treatment assessment. PET/CT, particularly with 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG), facilitates the visualization of glucose metabolism in the brain, enabling early diagnosis, staging, and monitoring of neurodegenerative disease progression. The advent of amyloid and tau PET imaging has further propelled the field forward, offering invaluable tools for tracking pathological hallmarks, assessing treatment response, and predicting clinical outcomes. While some therapeutic interventions targeting amyloid plaque load showed promising results with the reduction of cerebral amyloid accumulation over time, others failed to demonstrate a significant impact of anti-amyloid agents for reducing the amyloid plaques burden in AD brains. Tau PET imaging has conversely fueled the advent of disease-modifying therapeutic strategies in AD by supporting the assessment of neurofibrillary tangles of tau pathology deposition over time. Looking ahead, PET imaging holds immense promise for studying additional targets such as neuroinflammation, cholinergic deficit, and synaptic dysfunction. Advances in radiotracer development, dedicated brain PET/CT scanners, and Artificial Intelligence-powered software are poised to enhance the quality, sensitivity, and diagnostic power of molecular neuroimaging. Consequently, PET/CT remains at the forefront of AD research, offering unparalleled opportunities for unravelling the complexities of the disease and advancing therapeutic interventions, although it is not yet enough alone to allow patients’ recruitment in therapeutic clinical trials.
Treating Alzheimer’s Disease: Focusing on Neurodegenerative Consequences
Authors: Sun Miao-Kun , Alkon Daniel L.
Published: October 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: October 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.
Exploring the evolution of rotavirus vaccines and its impact on global public health
Authors: Badge Ankit K. , Bankar Nandkishor J. , Tiwade Yugeshwari R. , Bandre Gulshan R. , Holkar Ghoshita
Published: October 2024

Rotavirus, a prevalent pathogen within the Reoviridae family, poses a significant threat to children, particularly infants and young children, causing gastroenteritis. High transmissibility and severe diarrhea lead to dehydration, severe infection, and death, especially in regions with limited resources and poor sanitation. Rotavirus infections spread through contaminated food, water, and fomites, primarily affecting developing countries due to inadequate sanitation standards. Vaccination has emerged as a crucial preventive strategy against rotavirus gastroenteritis, with the aim of reducing the global burden of the disease. The early rotavirus vaccines, exemplified by Rota-Shield, faced challenges such as safety concerns, emphasizing the importance of rigorous safety evaluation and post-marketing surveillance. Subsequent vaccines, Rotarix and RotaTeq, have shown efficacy and safety, significantly reducing rotavirus-related morbidity and mortality worldwide. The global implementation of rotavirus vaccination programs has expanded vaccine access, leading to a decrease in disease incidence and hospitalizations. Despite these achievements, challenges persist, such as hesitantness to apply the vaccine and disparities in vaccine access. Future research directions include the development of next-generation vaccines with greater coverage and the exploration of novel vaccine delivery strategies. A sustained commitment to research, infrastructure strengthening, and community involvement is essential to eliminate the burden of rotavirus disease worldwide. The objective of this review is to explore the evolution of rotavirus vaccines and impact on global public health.