bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Efficacy and Safety Using Low Dose Radiation Therapy with Alzheimer’s Disease: A Protocol for Multicenter Phase II Clinical Trial
Authors: Kim Dong-Yun , Kim Jae Sik , Seo Young-Seok , Park Woo-Yoon , Kim Byoung Hyuck , Hong Eun-Hee , Kim Ji Young , Cho Seong-Jun , Rhee Hak Young , Kim Aryun , Kim Keun You , Oh Dae Jong , Chung Weon Kuu 
Published: August 2023

Background: Alzheimer’s disease (AD), the most common cause of dementia, is a neurodegenerative disease resulting from extracellular and intracellular deposits of amyloid-β (Aβ) and neurofibrillary tangles in the brain. Although many clinical studies evaluating pharmacological approaches have been conducted, most have shown disappointing results; thus, innovative strategies other than drugs have been actively attempted. Objective: This study aims to explore low-dose radiation therapy (LDRT) for the treatment of patients with AD based on preclinical evidence, case reports, and a small pilot trial in humans. Methods: This study is a phase II, multicenter, prospective, single-blinded, randomized controlled trial that will evaluate the efficacy and safety of LDRT to the whole brain using a linear accelerator in patients with mild AD. Sixty participants will be randomly assigned to three groups: experimental I (24 cGy/6 fractions), experimental II (300 cGy/6 fractions), or sham RT group (0 cGy/6 fractions). During LDRT and follow-up visits after LDRT, possible adverse events will be assessed by the physician’s interview and neurological examinations. Furthermore, the effectiveness of LDRT will be measured using neurocognitive function tests and imaging tools at 6 and 12 months after LDRT. We will also monitor the alterations in cytokines, Aβ42/Aβ40 ratio, and tau levels in plasma. Our primary endpoint is the change in cognitive function test scores estimated by the Alzheimer’s Disease Assessment Scale-Korea compared to baseline after 6 months of LDRT. Conclusions: This study is registered at ClinicalTrials.gov [NCT05635968] and is currently recruiting patients. This study will provide evidence that LDRT is a new treatment strategy for AD.
Differences in the Cognitive Function of Mexican Adults Aged 60 and Older with Self-Reported Diabetes in 2001 and 2018
Authors: Camarillo Joe , Villarreal Rizzo Alan , Cabrero Castro Jose Eduardo , Downer Brian 
Published: August 2023

Background: The prevalence of type 2 diabetes in Mexico has nearly doubled for adults aged ≥60. Increases in education and healthcare resources to manage chronic conditions have contributed to population-level increases in the cognitive functioning of older adults. However, research has not focused on older adults with chronic conditions such as diabetes. Objective: Our objective was to compare the cognitive functioning of Mexican adults aged ≥60 with diabetes in 2001 and 2018. Methods: Data came from Mexican Health and Aging Study. Our study used a cross-sectional design and included participants aged ≥60 with self-reported diabetes during the 2001 ( n = 1,052, mean age = 68.4, female = 59.6%) and 2018 ( n = 2,469, mean age = 70.6, female = 62.0%) observation waves. Five cognitive tests were used to create a score of global cognition. Generalized estimating equations were used to compare global cognition in 2001 to 2018. Results: Older adults in 2018 had more education and were more likely than older adults in 2001 to take oral medication for diabetes, insulin, and to check blood sugar weekly. Older adults in 2018 had higher global cognition than in 2001 when adjusting for age, gender, education, and health insurance coverage ( b = 0.38, SE = 0.02). This statistically significant difference remained after adjusting for health conditions, health behaviors, and diabetes management behaviors. Conclusions: Older adults in Mexico with self-reported diabetes in 2018 had higher cognitive function than in 2001. Future research is needed to investigate causes of the cohort differences in cognitive functioning among Mexican older adults with self-reported diabetes.
Detecting Dementia by Saliva Analysis: A Fingerprinting Unobtrusive Method Based on a Fast and Cheap Sensor System
Authors: Di Gioia Claudia , Santonico Marco , Zompanti Alessandro , Sabatini Anna , Grasso Simone , Ursini Francesca , Pedone Claudio , Galdi Flavia , Antonelli Incalzi Raffaele , Pennazza Giorgio 
Published: August 2023

Background: Recent studies have shown that oxidative stress plays a relevant role in Alzheimer’s disease (AD), and in the pathogenesis of vascular dementia (VaD). New diagnostic methods look for biological samples with non-invasive sampling methods. Among these, saliva shows an increase in oxidative stress products, thus a corresponding reduction in antioxidant products were found in dementia cases compared to healthy controls. Compounds identified in saliva include some hydrocarbons whose production has been related to the presence of reactive oxygen species. Objective: The hypothesis is that the voltammetric analysis performed on saliva could be a useful test for diagnosing dementia, potentially discriminating between AD and VaD. Methods: A single-center observational study was conducted on patients referred to the dementia clinic in the Neurology area and healthy controls recruited in the Orthopedics area of the Campus Bio-Medico Hospital in Rome. The study was aimed at evaluating the discriminative properties of salivary voltammetric analysis between healthy subjects and patients with dementia and, as a secondary outcome, between AD and VaD. A total of 69 subjects were enrolled, including 29 healthy controls, 20 patients with AD, and 20 patients with VaD. The degree of cognitive impairment was classified on the basis of the Mini-Mental State Examination score. Results: The results obtained are promising, with an accuracy of 79.7%, a sensitivity of 82.5%, and a specificity of 75.8%, in the discrimination of dementia versus controls. Conclusions: The methods tested demonstrate to be relevant in the discrimination between dementia and controls. A confirmatory study is already running.
Spatiotemporal Characteristics of Regional Brain Perfusion Associated with Neuropsychiatric Symptoms in Patients with Alzheimer’s Disease
Authors: Jiang Jiwei , Wang Anxin , Liu Yaou , Yao Zeshan , Sun Mengfan , Jiang Tianlin , Li Wenyi , Jiang Shirui , Zhang Xiaoli , Wang Yanli , Zhang Yuan , Jia Ziyan , Zou Xinying , Xu Jun 
Published: August 2023

Background: Current technology for exploring neuroimaging markers and neural circuits of neuropsychiatric symptoms (NPS) in patients with Alzheimer’s disease (AD) is expensive and usually invasive, limiting its use in clinical practice. Objective: To investigate the cerebral morphology and perfusion characteristics of NPS and identify the spatiotemporal perfusion circuits of NPS sub-symptoms. Methods: This nested case-control study included 102 AD patients with NPS and 51 age- and sex-matched AD patients without NPS. Gray matter volume, cerebral blood flow (CBF), and arterial transit time (ATT) were measured and generated using time-encoded 7-delay pseudo-continuous arterial spin labeling (pCASL). Multiple conditional logistic regression analysis was used to identify neuroimaging markers of NPS. The associations between the CBF or ATT of affected brain areas and NPS sub-symptoms were evaluated after adjusting for confounding factors. The neural circuits of sub-symptoms were identified based on spatiotemporal perfusion sequencing. Results: Lower Mini-Mental State Examination scores ( p < 0.001), higher Caregiver Burden Inventory scores ( p < 0.001), and higher CBF ( p = 0.001) and ATT values ( p < 0.003) of the right anteroventral thalamic nucleus (ATN) were risk factors for NPS in patients with AD. Six spatiotemporal perfusion circuits were found from 12 sub-symptoms, including the anterior cingulate gyri-temporal pole/subcortical thalamus-cerebellum circuit, insula-limbic-cortex circuit, subcortical thalamus-temporal pole-cortex circuit, subcortical thalamus-cerebellum circuit, frontal cortex-cerebellum-occipital cortex circuit, and subcortical thalamus-hippocampus-dorsal raphe nucleus circuit. Conclusions: Prolonged ATT and increased CBF of the right ATN may be neuroimaging markers for detecting NPS in patients with AD. Time-encoded pCASL could be a reliable technique to explore the neural perfusional circuits of NPS.
Unleashing the Power of Bayesian Re-Analysis: Enhancing Insights into Lecanemab (Clarity AD) Phase III Trial Through Informed t-Test
Authors: Costa Tommaso , Premi Enrico , Liloia Donato , Cauda Franco , Manuello Jordi 
Published: August 2023

Background: Clinical trials targeting Alzheimer’s disease (AD) aim to alleviate clinical symptoms and alter the course of this complex neurodegenerative disorder. However, the conventional approach of null hypothesis significance testing (NHST) commonly employed in such trials has inherent limitations in assessing clinical significance and capturing nuanced evidence of effectiveness on a continuous scale. Objective: In this study, we conducted a re-analysis of the phase III trial of lecanemab, a recently proposed humanized IgG1 monoclonal antibody with high affinity for Aβ soluble protofibrils, using a Bayesian approach with informed t-test priors. Methods: To achieve this, we carefully selected trial data and derived effect size estimates for the primary endpoint, the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB). Subsequently, a series of Bayes Factor analyses were performed to compare evidence supporting the null hypothesis (no treatment effect) versus the alternative hypothesis (presence of an effect). Drawing on relevant literature and the lecanemab phase III trial, we incorporated different minimal clinically important difference (MCID) values for the primary endpoint CDR-SB as prior information. Results: Our findings, based on a standard prior, revealed anecdotal evidence favoring the null hypothesis. Additional robustness checks yielded consistent results. However, when employing informed priors, we observed varying evidence across different MCID values, ultimately indicating no support for the effectiveness of lecanemab over placebo. Conclusion: Our study underscores the value of Bayesian analysis in clinical trials while emphasizing the importance of incorporating MCID and effect size granularity to accurately assess treatment efficacy.
Characterising the Genetic Landscape of Amyotrophic Lateral Sclerosis: A Catalogue and Assessment of Over 1,000 Published Genetic Variants
Authors: McCann Emily P. , Grima Natalie , Fifita Jennifer A. , Chan Moi Fat Sandrine , Lehnert Klaus , Henden Lyndal , Blair Ian P. , Williams Kelly L. 
Published: August 2023

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with genetic and phenotypic heterogeneity. Pathogenic genetic variants remain the only validated cause of disease, the majority of which were discovered in familial ALS patients. While causal gene variants are a lesser contributor to sporadic ALS, an increasing number of risk alleles (low penetrance genetic variants associated with a small increase in disease risk) and variants of uncertain significance have been reported. Objective: To examine the pathogenic potential of genetic variation in ALS, we sought to characterise variant- and gene-level attributes of previously reported ALS-implicated variants. Methods: A list of 1,087 genetic variants reported in ALS to March 2021 was compiled through comprehensive literature review. Individual variants were annotated using in silico tools and databases across variant features including pathogenicity scores, localisation to protein domains, evolutionary conservation, and minor allele frequencies. Gene level attributes of genic tolerance, gene expression in ALS-relevant tissues and gene ontology terms were assessed for 33 ALS genes. Statistical analysis was performed for each characteristic, and we compared the most penetrant variants found in familial cases with risk alleles exclusive to sporadic cases, to explore genetic variant features that associate with disease penetrance. Results: We provide spreadsheet (hg19 and GRCh38) and variant call format (GRCh38) resources for all 1,087 reported ALS-implicated variants, including detailed summaries for each attribute. We demonstrate that the characteristics of variants found exclusively in sporadic ALS cases are less severe than those observed in familial ALS. Conclusions: We provide a comprehensive, literature-derived catalogue of genetic variation in ALS thus far and reveal crucial attributes that contribute to ALS pathogenicity. Our variant- and gene-level observations highlight the complexity of genetic variation in ALS, and we discuss important implications and considerations for novel variant interpretation.
LANDSCAPE ARCHITECTURE AS MEANS OF FORMING AN INCLUSIVE URBAN SPACE IN BUFFER ZONES OF CULTURAL HERITAGE OBJECTS
Authors: Matsokha Alina 
Published: August 2023

The article presents the results of the author's research on the formation of an inclusive urban space by means of landscape architecture; the legal framework is considered; the main principle of creating a network of barrier-free pedestrian routes in the space of the middle city is determined (the principle of "frame on the frame"); methods of implementing barrier-free (delimitation of pedestrian-transport traffic; zoning of pedestrian parts of the street with combinations of different types of paving by texture and color and others). Based on the analysis of world theoretical and practical experience, the means of implementing barrier-free (paving, gardening, decorating, etc.) have been determined and a number of examples in European cities have been provided. An algorithm for the formation of inclusive urban space in buffer zones of the second category of indirect multifunctional use of cultural heritage objects located in Ukraine has been proposed. Recommendations on the adaptation of public spaces to form an inclusive urban space within buffer zones have been provided.
According to the specifics of the architectural and landscape organization, the most difficult is the category of buffer zones "non-direct multifunctional usage" (according to I. Korotun). As this zone covers historical city centers, historical city areas and other areas occupied by residential and non-residential buildings thus, the priority function in this aspect arises the safety and comfort of people, and the Memorial Protection Object Facility acquires a secondary role. In Ukraine, 4 out of 8 World Heritage sites have buffer zones of non-direct multifunctional use ("Kyiv: St. Sophia Cathedral and nearby monastery buildings, Kyiv-Pechersk Lavra, Church of the Savior on Berestov" (1990); "Ensemble of the historical center of Lviv" (1998); "Residence of the Metropolitans of Bukovina and Dalmatia" (2011) and "Historical Center of Odesa" (2023)).
An analysis of world experience in the formation of an inclusive urban environment revealed that the main methods of implementing this approach are the creation of a network of barrier-free pedestrian routes in the space of the city center. Within the buffer zones, this can be done through: the delineation of pedestrian-transport traffic; zoning of pedestrian zones with combinations of different types of landscaping, decoration and types of paving by texture and color; selection of paving and equipment colors in accordance with the scale of buffer zone development; arrangement of unhindered ways of pedestrians movement by leveling surface differences taking into account the security requirements of a particular site.
FUNDAMENTALS OF URBAN PLANNING ORGANIZATION OF ENERGYEFFICIENT ECOLOGICAL SETTLEMENTS TAKING INTO ACCOUNT ENERGY EFFICIENCY INDICATORS
Authors: Selikhova Yana 
Published: August 2023

The article considers the basics of urban planning organization of energy-efficient ecological settlements (hereinafter - EEP) taking into account energy efficiency indicators, since the organization of these urban planning formations is a multifaceted process that is associated with various factors that are considered in various scientific fields.
Energy-efficient ecological settlements - can become one of the options for a comfortable ecological and energy-saving living environment (ensuring the necessary microclimatic conditions in buildings, using natural technologies in lighting and ventilation, sustainable construction of low-rise, semi-underground and underground construction, application of natural architecture techniques, selection of local and ecological materials, assessment of the life cycle of the building, provision of alternative energy sources), which can become a full-fledged living space with all the necessary conditions, starting from providing people with homes, ending with places of work.
The main aspects of the development of energy-efficient ecological settlements have been identified, including: - the aspect of the functional organization of the territory, taking into account orientation according to the sides of the world, landscape assessment of the territory, etc.;
- aspect of permaculture design; - landscape and composition aspect; - the aspect of ecological and autonomous construction (use of natural or recycled materials, design of an energy-saving building form); - the aspect of independence from energy resources (solar energy, wind energy, geothermal energy, wave energy and biomass); - aspect of water resources management (complex system of drinking water management and management of reclaimed water for irrigation and toilets, rainwater storage system, biological wastewater treatment system, flood control system). - aspect of waste utilization and recycling (processing of solid household waste, composting of organic and human waste, used as biogas for obtaining energy and fertilizers for agriculture); - the aspect of rational planning of transport links and the road-trail network for the use of ecological transport; - aspect of socio-economic development (eco-industry, tourism, educational programs and community values).
A unified structural model of EEP design has been developed. The unified structural model is a brief description of the stages of design (sequence of actions – algorithm) for further design, which includes four stages: Stage I – determination of the territory as an EEP, Stage II – determination of EEP factors, Stage III – analysis of initial data for further design, IV stage – design of EEP. Based on the results of the research, the stages of urban planning organization of energy-efficient ecological settlements were revealed, taking into account energy efficiency indicators (on the example of the Kharkiv region), which are presented in the form of detailed schemes.
REGARDING THE CURRENT STATE OF URBAN PLANNING AND REGIONAL ACTIVITIES IN UKRAINE
Authors: Demin Mykola , Yatsenko Viktor , Berova Polina 
Published: August 2023

This research paper examines the peculiarities of urban and regional planning activities in modern conditions. The importance of studying the preliminary stages of project research and educational activities that form a sustainable basis for urban planning and regional planning is considered: the field of economics, sociology, geography, ecology and engineering.
It is determined how the instability of their development affects the sustainable development of the human-environmental settlement system as a whole. The existing forms of settlement, such as settlement, suburban, group-territorial community, and their place in the general system of settlement - region, country - are considered. As a strategy of modern development, the paper considers the process of sociologization of the space in which society lives.
The current state of public interests in the space in which people live, work, and rest is considered. The main legislative and regulatory institutions of the advanced European countries that have managed to put urban planning and regional activities as one of the main prospects for development are presented.
The importance of creating the Urban Planning Code of Ukraine as a sustainable law is beyond doubt. The author proposes a model of planning organization of Ukraine in the structure of the European space as a model of integration. The main challenges of today's society to urban planning activities are formed: competitiveness, environmental friendliness, mobility, sociologization, sustainable urbanization. At the heart of the challenges posed by today's urban planning activities should always be a person and the space in which he or she organizes his or her existence.
INNOVATIVE METHOD FOR STUDYING THE DYNAMICS OF POLLUTION AND HUMIDITY CHANGES IN SPORTS FACILITIES: FITNESS ROOMS AND SWIMMING POOLS
Authors: Chоvniuk Yuriy , Cherednichenko Petro , Moskvitina Anna , Zolotar Luydmula 
Published: August 2023

It is necessary to take into account the reaction time of the system to changes and provide for changes in parameters when using modern automation systems and indoor microclimate control with a dynamic change in the intake of harmful substances. The change in carbon dioxide (CO2) pollution and air humidity in sports facilities, such as fitness rooms and swimming pools, is a non-stationary random process with a complex type of non-stationarity and can be described by statistical characteristics. Obtaining these statistical characteristics is complicated by the probabilistic nature of the whole process and the presence of random systematic errors in measuring pollution (CO2) and air humidity of a particular sports facility, the specifics of the functioning of heat and mass transfer processes, moisture exchange in the premises of sports facilities (swimming pools, fitness halls, gyms, etc.). etc.) and has not been studied in modern scientific literature. Therefore, this study was carried out precisely in order to improve the situation and bring it out of the impasse (uncertainty) regarding sports facilities and premises for mass physical culture, recreation, and leisure. The paper proposes a comprehensive method for studying the dynamics of changes in pollution (CO2) and air humidity in a sports facility (fitness rooms, swimming pools, etc.). It allows you to determine the statistical characteristics of the process and identify it with an accuracy that is satisfactory for practical purposes (the error is no more than 10%). In the process of research, it is necessary to use daily diagrams of the operation of CO2 air pollution meters and moisture meters in fitness rooms and swimming pools for a long period of time (70 days). An optimal flow meter of air pollution with carbon dioxide (CO2) or a moisture meter should be built according to a discrete circuit with digital processing of information that comes from a sensor (an artificial intelligence system for controlling air gas exchange processes in a sports facility), according to an algorithm for determining a moving average over a period of 10 ... 20 minutes averaging of the signal and the interval for issuing results 2 ... 5 min. This is what will make it possible to reduce random measurement errors and ensure accurate reproduction of the dynamics of the processes of changing Ac(t) or Wp(t) (which, by the way, can be quite fleeting).