bluuebunny/crossref_metadata_2025 huggingface dataset:
Features of the Digitalization of the Educational Process in a Sports Higher Education Institutions
Authors: Zakharova Akulina E. , Alekseeva Galina Gavrilievna , Yavlovskaya Praskovya Egorovna
Published: December 2022

The article deals with the peculiarities of distance learning organisation in a sport higher education institution during the pandemic. The subject of the study is the process of distance learning organisation in higher education institute during the period of COVID-19 restrictive measures. The Churapchinsky State Institute of Physical Culture and Sport is one of the first higher education institutions located in a rural environment, with more than 90% of its students coming from the heritage and districts of the Republic of Sakha (Yakutia). The specifics of higher education institute imply a large volume of practical training sessions and daily training in selected sports in equipped sports facilities. The distance learning format has made significant adjustments to the content and forms of practical training, in particular student sports training. A total of 320 full-time and part-time students from 7 areas of study took part in the survey. The results revealed the degree of students' readiness for the transition to distance learning, assessment of the possibility of full training for credit-examination session and state final attestation, features of practical training in elective courses of physical education and sports disciplines, the level of satisfaction, advantages and disadvantages in the organization of distance learning in higher education institution. The results of the study can be used to improve the organisation of distance learning in higher education institutions, while maintaining the quality and accessibility of the educational process. The novelty of the study lies in the investigation of the organisation of the distance learning format and the attitudes towards it of the students of a physical education institution located in a rural area. It has been established that the transition of the educational process to a fully distance format in a sports university has intensified the resources of the institute, forcing the use of information technology in training, while revealing certain difficulties.
Polluted aquifer inverse problem solution using artificial neural networks
Authors: Foddis Maria Laura , Uras Gabriele , Ackerer Philippe , Montisci Augusto
Published: December 2022

The problem of identifying an unknown pollution source in polluted aquifers, based on known contaminant concentrations measurement in the studied areas, is part of the broader group of issues, called inverse problems. This paper investigates the feasibility of using Artificial Neural Networks (ANNs) for solving the inverse problem of locating in time and space the source of a contamination event in a homogeneous and isotropic two dimensional domain. ANNs are trained in order to implement an input-output relationship which associates the position. Once the output of the system is known, the input is reconstructed by inverting the trained ANNs. The approach is applied for studying a theoretical test case where the inverse problem is solved on the basis of measurements of contaminant concentrations in monitoring wells located in the studied area. Groundwater pollution sources are characterized by varying spatial location and duration of activity. To identify these unknown pollution sources, concentration measurements data of monitoring wells are used. If concentration observations are missing over a length of time after an unknown source has become active, it is more difficult to correctly identify the unknown pollution source. In this work, a missing data scenario has been taken into consideration. In particular, a case where only one measurement has been made after the pollutant source interrupted its activity has been considered.
Di Apollo e di alcune fondazioni seleucidi
Authors: Biagetti Claudio
Published: December 2022

This paper questions the widespread view associating the Apollo’s epithet ἀρχηγέτης/ἀρχηγός with the Seleucid city foundations in the Greek East. Special attention is paid to the epigraphic and numismatic evidence coming from the poleis of Apameia in Syria and Hierapolis of Phrygia, where Apollo was honoured as divine ἀρχηγέτης in imperial times. A reassessment of the available sources does not substantiate the claim that the mention of Apollo Ἀρχηγέτης in the inscriptions from Apameia, Hierapolis and other cities of the Greek East automatically points to cults going back to the Seleucid period.
Desmosomal connectomics of all somatic muscles in an annelid larva
Authors: Jasek Sanja , Verasztó Csaba , Brodrick Emelie , Shahidi Réza , Kazimiers Tom , Kerbl Alexandra , Jékely Gáspár
Published: December 2022

Cells form networks in animal tissues through synaptic, chemical, and adhesive links. Invertebrate muscle cells often connect to other cells through desmosomes, adhesive junctions anchored by intermediate filaments. To study desmosomal networks, we skeletonised 853 muscle cells and their desmosomal partners in volume electron microscopy data covering an entire larva of the annelid Platynereis. Muscle cells adhere to each other, to epithelial, glial, ciliated, and bristle-producing cells and to the basal lamina, forming a desmosomal connectome of over 2000 cells. The aciculae – chitin rods that form an endoskeleton in the segmental appendages – are highly connected hubs in this network. This agrees with the many degrees of freedom of their movement, as revealed by video microscopy. Mapping motoneuron synapses to the desmosomal connectome allowed us to infer the extent of tissue influenced by motoneurons. Our work shows how cellular-level maps of synaptic and adherent force networks can elucidate body mechanics.
Modeling the spatiotemporal spread of beneficial alleles using ancient genomes
Authors: Muktupavela Rasa A , Petr Martin , Ségurel Laure , Korneliussen Thorfinn , Novembre John , Racimo Fernando
Published: December 2022

Ancient genome sequencing technologies now provide the opportunity to study natural selection in unprecedented detail. Rather than making inferences from indirect footprints left by selection in present-day genomes, we can directly observe whether a given allele was present or absent in a particular region of the world at almost any period of human history within the last 10,000 years. Methods for studying selection using ancient genomes often rely on partitioning individuals into discrete time periods or regions of the world. However, a complete understanding of natural selection requires more nuanced statistical methods which can explicitly model allele frequency changes in a continuum across space and time. Here we introduce a method for inferring the spread of a beneficial allele across a landscape using two-dimensional partial differential equations. Unlike previous approaches, our framework can handle time-stamped ancient samples, as well as genotype likelihoods and pseudohaploid sequences from low-coverage genomes. We apply the method to a panel of published ancient West Eurasian genomes to produce dynamic maps showcasing the inferred spread of candidate beneficial alleles over time and space. We also provide estimates for the strength of selection and diffusion rate for each of these alleles. Finally, we highlight possible avenues of improvement for accurately tracing the spread of beneficial alleles in more complex scenarios.
Cross-talk between red blood cells and plasma influences blood flow and omics phenotypes in severe COVID-19
Authors: Recktenwald Steffen M , Simionato Greta , Lopes Marcelle GM , Gamboni Fabia , Dzieciatkowska Monika , Meybohm Patrick , Zacharowski Kai , von Knethen Andreas , Wagner Christian , Kaestner Lars , D'Alessandro Angelo , Quint Stephan
Published: December 2022

Coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and can affect multiple organs, among which is the circulatory system. Inflammation and mortality risk markers were previously detected in COVID-19 plasma and red blood cells (RBCs) metabolic and proteomic profiles. Additionally, biophysical properties, such as deformability, were found to be changed during the infection. Based on such data, we aim to better characterize RBC functions in COVID-19. We evaluate the flow properties of RBCs in severe COVID-19 patients admitted to the intensive care unit by using microfluidic techniques and automated methods, including artificial neural networks, for an unbiased RBC analysis. We find strong flow and RBC shape impairment in COVID-19 samples and demonstrate that such changes are reversible upon suspension of COVID-19 RBCs in healthy plasma. Vice versa, healthy RBCs resemble COVID-19 RBCs when suspended in COVID-19 plasma. Proteomics and metabolomics analyses allow us to detect the effect of plasma exchanges on both plasma and RBCs and demonstrate a new role of RBCs in maintaining plasma equilibria at the expense of their flow properties. Our findings provide a framework for further investigations of clinical relevance for therapies against COVID-19 and possibly other infectious diseases.
The Icelandic harbour seal (Phoca vitulina) population: trends over 40 years (1980–2020) and current threats to the population.
Authors: Granquist Sandra Magdalena
Published: December 2022

Regular harbour seal (Phoca vitulina) population censuses are necessary to monitor fluctuations in the population size and to inform seal management. In this paper, the status of the Icelandic harbour seal population is presented, along with trends in the population over a 40-year period. In total, 13 full aerial censuses were carried out during the moulting season (July-August) between 1980 and 2020. The most recent census from 2020 yielded an estimate of 10,319 (CI 95%= 6,733-13,906) animals, indicating that the population is 69.04% smaller than when systematic monitoring of the population commenced in 1980 (33,327 seals). The observed decrease puts the population on the national red list for threatened populations. Trend analyses indicate that most of the decline occurred during the first decade, when the population decreased about 50% concurrently with large human induced removals of harbour seals. After that point, the population decline slowed down but continued, and currently the population seems to fluctuate around a stable minimum level. The sensitive conservation status of the population underlines the need to assess and sustainably manage current threats to the population, including human induced removals, anthropogenic disturbance, and various environmental factors such as contaminants, climate change and fluctuation in prey availability. Furthermore, it is urgent to continue regular censuses and to increase monitoring of population demographic factors.
The voice of Twitter: observable subjective well-being inferred from tweets in Russian
Authors: Smetanin Sergey , Komarov Mikhail
Published: December 2022

As one of the major platforms of communication, social networks have become a valuable source of opinions and emotions. Considering that sharing of emotions offline and online is quite similar, historical posts from social networks seem to be a valuable source of data for measuring observable subjective well-being (OSWB). In this study, we calculated OSWB indices for the Russian-speaking segment of Twitter using the Affective Social Data Model for Socio-Technical Interactions. This model utilises demographic information and post-stratification techniques to make the data sample representative, by selected characteristics, of the general population of a country. For sentiment analysis, we fine-tuned RuRoBERTa-Large on RuSentiTweet and achieved new state-of-the-art results of F1 = 0.7229. Several calculated OSWB indicators demonstrated moderate Spearman’s correlation with the traditional survey-based net affect (rs = 0.469 and rs = 0.5332, p < 0.05) and positive affect (rs = 0.5177 and rs = 0.548, p < 0.05) indices in Russia.
Influence of long-term participation in amateur sports on physical posture of teenagers
Authors: Huang Yongchao , Zhai Meiling , Zhou Shi , Jin Yahong , Wen Li , Zhao Yuqi , Han Xu
Published: December 2022

Aim

The aim of this cross-sectional study was to explore the influence of long-term participating in amateur sports on body posture of school students.

Methods

A survey on sport participation was conducted on 1,658 volunteer students aged from 6 to 17 years in two primary schools and one meddle school in Tianjin city. The PA200LE body posture evaluation system and a SpineScanSH-115 electronic spine measuring instrument were used to assess the participants’ body posture. According to the survey results and against the inclusion and exclusion criteria, 1,124 eligible participants were divided into seven sport participation groups and seven age-matched control groups for statistical comparisons.

Results

Compared with the age-matched controls, the natural standing thoracic kyphosis angle of the swimming group (35.0 ± 9.5 VS 31.2 ± 8.5; t =  − 2.560; p = 0.011) and the football group (34.6 ± 7.2 VS 31.9 ± 7.5; t =  − 2.754; p = 0.006) were found to be significantly larger; the natural standing lumbar lordosis angle (−23.0 ± 11.0 VS −27.0 ± 11.1; t = 0.344; p = 0.024) and the upright sitting lumbar lordosis angle (−11.7 ± 8.4 VS −15.2 ± 12.3; t = 5.738; p = 0.030) of the swimming group was significantly smaller; the upright sitting thoracic kyphosis angle of the running group (25.1 ± 9.3 VS 22.6 ± 9.9; t =  − 1.970; p = 0.050) was significantly larger; the upright sitting thoracic kyphosis angle (23.9 ± 8.9 VS 27.0 ± 7.6; t = 2.096; p = 0.038), the learning position thoracic kyphosis angle (31.0 ± 8.6 VS 37.1 ± 8.9; t = 3.076; p = 0.003), the shoulder level (−1.3 ± 2.1 VS 0.0 ± 2.5; t = 2.389; p = 0.019) and waist level (−1.2 ± 1.7 VS −0.3 ± 1.7; t = 2.511; p = 0.013) of the table tennis group were significantly smaller.

Conclusions

The results showed that long-term participation in recreational sports training had an impact on the physical posture of adolescents.
The role of termites as ecosystem engineers in southern African drylands: overlooked, underestimated, misinterpreted
Authors:   University of Hamburg, Schmiedel Ute , Finckh Manfred
Published: December 2022

Editorial
Not one but several: Morphological diversity within the sand termite
Authors:   University of Hamburg, Gunter Felicitas , Oldeland Jens , Henschel Joh R. , Picker Mike D. , Jürgens Norbert
Published: December 2022

Termite species are generally identified based on morphological differences of soldiers. This approach is here applied for the sand termite species Psammotermes allocerus. By using high quality resolution images, measurements of 26 traits of head, labrum and mandibles, the CART method, as well as geometric-morphometric shape analyses of mandibles of large soldiers (> 7mm in total body lengths) a discrimination between soldiers of three geographical regions is possible. Soldiers collected from the Succulent Karoo, Southern Namib and Northern Namib differ significantly from each other. This study is a first attempt to show strong morphological variation and differentiation within the sand termite Psammotermes allocerus from the arid regions. Further research in additional geographical regions and the comparison of different development stages of soldiers are needed for a complete assessment of the morphological diversity of species.
Meeting notes
Authors: - -
Published: December 2022

Meeting notes for 11 March 1895.
Titularidade dos Direitos Autorais nas Criações com Aplicação da Inteligência Artificial
Authors: Rocha Uelisson Borges , Saldanha Cleiton Braga , Lima Ângela Maria Ferreira , Pereira Aliger dos Santos
Published: December 2022

Com o atual cenário da transformação digital, está cada vez mais recorrente a criação de obras resultantes da aplicação da Inteligência Artificial. Diante desse fato, questiona-se quem detém a titularidade dos direitos autorais dessas criações. Este artigo tem como objetivo discutir quem deve ser o titular dos direitos autorais das criações com a aplicação da Inteligência Artificial. Trata-se de uma abordagem qualitativa, a partir de uma pesquisa exploratória, utilizando-se da análise bibliométrica, a fim de se realizar uma reflexão sobre a temática. Diante dos resultados encontrados, verificou-se que a discussão ainda é recente e que a legislação brasileira é silente quanto a essa definição. Por fim, conclui-se por sugerir a ampliação da proteção já conferida pelos direitos autorais para abarcar também as criações decorrentes da utilização da Inteligência Artificial.
Leptin accelerates BMSC transformation into vertebral epiphyseal plate chondrocytes by activating SENP1‐mediated deSUMOylation of SIRT3
Authors: Li Xiaomiao , Fu Xiaodong , Li Hao , Gao Yingjian , Wang Weili , Liu Zude , Shen Yi
Published: December 2022

Bone marrow mesenchymal stem cells (BMSCs) are capable of multidirectional differentiation, and engrafted BMSCs can be used to replace damaged chondrocytes for treatment of intervertebral disc disease. However, chondroblast differentiation of implanted BMSCs is inhibited by the anoxic environment of the articular cavity. Here, we found that leptin enhanced the transformation of BMSCs into chondrocytes under hypoxic conditions. BMSCs isolated from mice were cultured in medium supplemented with leptin under hypoxia. The expression of MFN1/2 and OPA1 were increased only in BMSCs cultured in an anoxic environment. In addition, in hypoxic environments cell energy metabolism relies on glycolysis regulated by leptin, rather than by mitochondrial oxidation. The expression of the de‐SUMOylation protease SENP1 was elevated, leading to SIRT3‐mediated activation of PGC‐1α; these processes were regulated by CREB phosphorylation, and promoted mitochondrial fusion and cell differentiation. The chondrogenic activity of BMSCs isolated from SIRT3‐knockout mice was lower than that of BMSCs isolated from wildtype mice. Implantation of SIRT3‐knockout murine‐derived BMSCs did not significantly improve the articular cartilage layer of the disc. In conclusion, the hypoxic microenvironment promoted BMSC differentiation into chondrocytes, whereas osteoblast differentiation was inhibited. SENP1 activated SIRT3 through the deSUMOylation of mitochondria and eliminated the antagonistic effect of SIRT3 acetylation on phosphorylation. When phosphorylation activity of CREB was increased, phosphorylated CREB is then transferred to the nucleus, affecting PGC‐1α. This promotes mitochondrial fusion and differentiation of BMSCs. Leptin not only maintains chondrogenic differentiation homeostasis of BMSCs, but also provides energy for differentiation of BMSCs under hypoxic conditions through glycolysis.
Nanoparticles of folic acid‐methyl‐β‐cyclodextrin (FA‐MβCD)/adamantane‐albumin exhibit enhanced antitumor activity compared with FA‐MβCD alone
Authors: Sakai Aiko , Yamashita Yuki , Misumi Shogo , Kishimoto Naoki , Onodera Risako , Higashi Taishi , Arima Hidetoshi , Motoyama Keiichi
Published: December 2022

Supramolecular drug carriers are a promising approach for delivering anticancer drugs with high blood retention after administration. We previously synthesized folic acid‐modified methyl‐β‐cyclodextrin (FA‐MβCD) as an anticancer drug. FA‐MβCD has a selective autophagy‐mediated antitumor effect on folic acid receptor (FR)‐expressing cancer cells. Here, we enhanced the antitumor effect and safety of FA‐MβCD by preparing a supramolecular nanoparticle formulation of FA‐MβCD via host–guest interactions using an adamantane conjugate with human serum albumin (Ad‐HSA). The Ad‐HSA/FA‐MβCD supramolecular complex prolonged the blood retention of FA‐MβCD and improved its antitumor effect and safety after intravenous administration in tumor‐bearing mice xenografted with FR‐expressing cancer cells. These results suggest that the supramolecular technique using Ad‐HSA is a promising approach for the delivery of CD‐based anticancer drugs.
Correctional English as a second language literacy for male Latino parents
Authors: Mercado Norma
Published: December 2022

This qualitative study examines Latino Spanish‐speaking inmates' participation in an English literacy project. The research questions were: What is the impact of the project on the participants’ literacy development? How does a Latino literacy project for Spanish‐speaking inmates facilitate parent engagement? Data collection included qualitative questionnaires, participant journal entries, attendance sheets, field notes, and interviews with male inmate parents. This study provides adult educators working with inmates a closer look at the impact of culturally relevant programs and supports the need to offer diverse programs for Spanish‐speaking inmates.
Drug Self‐Delivery Systems: Molecule Design, Construction Strategy, and Biological Application
Authors: Liu Chengfei , Liu Caiping , Bai Yang , Wang Jingxia , Tian Wei
Published: December 2022

Drug self‐delivery systems (DSDSs) offer new ways to create novel drug delivery systems (DDSs). In typical DSDSs, therapeutic reagents are not considered passive cargos but active delivery agents of actionable targets. As an advanced drug delivery strategy, DSDSs with positive cooperativity of both free drugs and nanocarriers exhibit the clear merits of unprecedented drug‐loading capacity, minimized systemic toxicity, and flexible preparation of nanoscale deliverables for passive targeted therapy. This review highlights the recent advances and future trends in DSDSs on the basis of two differently constructed structures: covalent and noncovalent bond‐based DSDSs. Specifically, various chemical and architectural designs, fabrication strategies, and responsive and functional features are comprehensively discussed for these two types of DSDSs. In addition, additional comments on the current development status of DSDSs and the potential applications of their molecular designs are presented in the corresponding discussion. Finally, the promising potential of DSDSs in biological applications is revealed and the relationship between preliminary molecular design of DSDSs and therapeutic effects of subsequent DSDSs biological applications is clarified.
High‐Efficiency and Mechanically Robust All‐Polymer Organic Photovoltaic Cells Enabled by Optimized Fibril Network Morphology
Authors: Ma Lijiao , Cui Yong , Zhang Jianqi , Xian Kaihu , Chen Zhihao , Zhou Kangkang , Zhang Tao , Wang Wenxuan , Yao Huifeng , Zhang Shaoqing , Hao Xiaotao , Ye Long , Hou Jianhui
Published: December 2022

All‐polymer organic photovoltaic (OPV) cells possessing high photovoltaic performance and mechanical robustness are promising candidates for flexible wearable devices. However, developing photoactive materials with good mechanical properties and photovoltaic performance so far remains challenging. In this work, a polymer donor PBDB‐TF with a high weight‐average molecular weight (Mw) is introduced to enable highly efficient all‐polymer OPV cells featuring excellent mechanical reliability. By incorporating the high‐Mw PBDB‐TF as a third component into the PBQx‐TF:PY‐IT blend, the bulk heterojunction morphology is finely tuned with a more compact π–π stacking distance, affording efficient pathways for charge transport as well as mechanical stress dissipation. Hence, all‐polymer OPV cells based on the ternary blend film demonstrate a maximum power conversion efficiency (PCE) of 18.2% with an outstanding fill factor of 0.796. The flexible OPV cell delivers a decent PCE of 16.5% with high mechanical stability. These results present a promising strategy to address the mechanical properties and boost the photovoltaic performance of all‐polymer OPV cells.
How the Eurasian Jay Expands its Color Palette by Optimizing Multiple Scattering
Authors: Jeon Deok‐Jin , Ji Seungmuk , Lee Eunok , Kang Jihun , D'Alba Liliana , Shawkey Matthew D. , Yeo Jong‐Souk
Published: December 2022

The production of structural color in nature is still incompletely understood. Multiple scattering exerts critical effects on synthetic disordered systems, but its effects on structural colors in natural materials are not yet well known. Here, electron microscopy, optical modeling, and biomimicry are used to show that variation in the thickness of the feather nanostructures creates periodic color variations in Eurasian jay wing covert feathers, with nanostructures within white feather regions being two times thicker than those in blue portions. This finding reveals that multiple scattering expands the natural color palette of the Eurasian jay by extending reflection to longer wavelengths in thicker spongy layers. Furthermore, it is found that the white color of Eurasian jay feathers is produced even in the presence of melanin due to a sufficiently thick spongy layer reflecting all visible wavelengths. Inspired by the Eurasian jay design solution, a one‐step self‐assembly method for mimicking periodic color variations in a synthetic context is described. Thus, the colors of natural color‐producing materials are modulated by changing only the thickness of the materials, leading to multiple scattering effects.
Ion‐specific effects in confined nanochannels and neural network
Authors: Wei Weichen , Wang Xuejiao
Published: December 2022

Since the discovery of biological ion channels and their role in physiology, scientists have been trying to create artificial structures that mimic biological ion channels. Nanochannels such as biological/solid‐state nanopores and porous nanostructures can have fine‐tuned ion behaviors in a confined space where ions are “aggregated”. Thus, one of the most exciting applications of nanochannels is artificial neurons and neural network based on the ion‐specific effects and nanofluidics. In this review article, it is the first time that the ion aggregation behaviors inside the confined nanochannels are summarized, and their connection to neuroscience, especially the artificial neurons and neural network, is explored and envisioned.
Automatic Prediction of Metal–Oxide–Semiconductor Field‐Effect Transistor Threshold Voltage Using Machine Learning Algorithm
Authors: Choi Seoyeon , Park Dong Geun , Kim Min Jung , Bang Seain , Kim Jungchun , Jin Seunghee , Huh Ki Seok , Kim Donghyun , Mitard Jerome , Han Cheol E. , Lee Jae Woo
Published: December 2022

A fast and precise threshold voltage (Vth) extraction method is required for the process design of electronic systems using metal–oxide–semiconductor field‐effect transistors (MOSFETs) and its immediate on‐site analysis during fabrication. The selection of a suitableVthextraction method is a complicated task because it involves a trade‐off between accuracy and simplicity according to the device scheme. Herein, an automatic‐prediction method of the MOSFETVthusing machine learning (ML) is proposed. The ML model is trained withVth, extracted using different methods (2nd derivative, constant current, andY‐function) and from various kinds of FETs (finFET, 2D FET, and metal–oxide thin‐film transistors). The concept of threshold ratio (Rth) for universalVthprediction, which considers the normalizedVthwithin certainVGranges, is suggested. The precision and accuracy of ML models are statistically verified by calculating the root mean square error (RMSE), mean absolute error, and mean coefficients of determination (R2) values. The universal ML model (k‐nearest neighbor (kNN)) achieves 1.35% of RMSE and 0.98 ofR2for the best score. The ML model eliminates the ambiguity inVthextraction and provides objectiveVthprediction for most FET schemes used in the semiconductor industry and research field.
Roles and Implications of Palindromic DNA in Alzheimer's Disease: A Systematic Review and Computational Analysis
Authors: Chen Yuqing
Published: December 2022

Background

A palindrome in DNA is a sequence consisting of two adjacent identical or highly similar inverted repeats. Palindromes are distributed throughout the genome and play important roles in gene expression and regulation. Palindromic mutations are linked to many disease states, such as neuronal disorders, mental retardation, and various cancers.

Method

A systematic review was conducted in which existing literature on the palindromic DNA within disease‐associated loci of AD is synthesised. Subsequent computational analysis of DNA palindromes within promoters, introns, and exons were characterised and discussed.

Result

Studies included in the review identified palindromes and palindrome‐altering in the causative genes associated with AD, which may influence the fine tuning of APP and PSEN gene expression and/or alternative splicing of the transcript, leading to their different susceptibilities to beta‐amyloidosis. Results of computational analysis suggested roles in transcription factor binding and regulatory control within promoters, alongside implications for vulnerability of palindromic regions to genomic variation within introns. Mutations in intronic regions may introduce novel regulatory activity and affect splice sites. Comparisons with the mice genome showed differential tolerance of longer unstable palindromic sequences.

Conclusion

Overall, the results from this study serve as a resource of identified AD‐associated palindromic sequences, which could affect various cellular processes leading to gene dysregulation and AD pathogenesis. Further research is warranted to enlighten their roles in the specific disease mechanism.
Culturally and linguistically appropriate home visit intervention for underserved dementia family caregivers: Preliminary results from a randomized controlled trial
Authors: Lee Jung‐Ah , Ju Eunae , Zhang Jiuchen , Sabino‐Laughlin Eilleen , Rahmani Amir , Gibbs Lisa , Shin Sanghyuk , Qu Annie , Kehoe Priscilla , Nyamathi Adey
Published: December 2022

Background

Family caregivers of persons with dementia (PWD) suffer from stress and negative health outcomes related to round‐the‐clock caregiving responsibilities. Often caregivers lack awareness of community resources. Community Health Workers (CHW) have proven effective in educating families and can implement interventions that aim to reduce the impact of stress on their health. To alleviate caregiver burden among dementia family caregivers, this study has CHWs’ visit family caregivers’ homes offering education, stress reduction, and compassionate support/listening.

Methods

Participants were recruited from Southern California via non‐profit organizations, senior centers, and adult day services. Participants were randomly assigned to CHW home‐visit intervention group (IG) or control group (CG) with resource information only. The intervention includes stress reduction techniques of mindful breathing and compassionate support/listening, (2) education on dementia caregiving skills to handle difficult behaviors of PWD, and (3) resource information. The 3‐month intervention is given by bilingual CHWs who speak English, Spanish, Vietnamese, or Korean. A linear mixed model was used to compare differences from baseline to 3‐month on each outcome (caregiver burden, PWD behaviors ‐ memory, distress, disruption) between IG and CG. Exit interviews were conducted for IG participants.

Results

26 family caregivers participated in the study (12 Korean, 9 Vietnamese, 3 Hispanic, 2 Caucasian); 14 spouses (54%), 12 off‐spring (46%); 18 females (69%), age from 34 to 89 (mean = 66.8 sd = 12.6). IG Participants showed a significant decrease in caregiving burden compared to CG (coefficient = ‐7.68, p = .0041). PWD behaviors were significantly decreased from baseline to 3 months but no difference by group. However, there was a trend for improvement of PWD’s memory problems in the IG compared to the CG (coefficient = ‐2.43, p = .056). Language specific exit interviews showed that educational materials were valuable and communication skills training was helpful as was CHW home visits. Most participants reported the benefit of mindful breathing and practiced it when overwhelmed or having sleep problems. The overall satisfaction of the intervention was high (mean = 4.4 of 5). Recruitment is on‐going but challenging during the pandemic.

Conclusion

Preliminary results showed the CHW led home‐visit intervention helped improve burden and PWD memory problems and was acceptable by the family caregivers of PWD.
Genetic and socioeconomic modulation of biomarkers
Authors: Yokoyama Jennifer S. , Piña‐Escudero Stefanie Danielle
Published: December 2022

Introduction

Identification and measurement of biomarkers has become a key component of much research in the neurodegeneration field, particularly in research linking psychosocial stressors and brain health. Socioeconomic position may influence neurodegeneration through several pathways, including behaviors and psychosocial stress levels, both of which may influence biological markers of inflammation, coagulation, and adhesion. Underserved populations, particularly from low‐to‐middle‐income countries in Latin America (LMICs), are more likely to have experienced poor, chronic stress due to discrimination, limited educational and occupational opportunities, and minimal access to social support and health care. All of these factors can modify neurodegenerative disease risk and clinical progression of dementia, in part through changes in immune function. Complicating matters, few studies have characterized inflammatory biomarker levels in LMICs, where biological and environmental exposures likely modify immune profiles. Finally, the effect of complex genetic admixture on both baseline and disease‐associated inflammatory biomarker levels remains underexplored, greatly limiting the generalizability of dementia biomarkers (beta amyloid, tau, neurofilament) that were largely developed in homogenous populations.

Method

We propose to review the existing evidence and present our ongoing study fostered in the Multi‐Partner Consortium to Expand Dementia Research in Latin America (ReDLat) cohort divided into three groups: participants with Alzheimer´s Dementia (AD), participants with Frontotemporal Dementia (FTD), and controls. We will comprehensively assess gene and protein expression measures of immune function in blood to identify single and combined measurements that provide sensitive and specific distinction between AD and FTD and all cases from controls. In addition, we will assess the modulatory effect that social determinants of health (SDOH) have on these biological biomarkers.

Expected Results

Our expected outcome is to understand how SDOH contribute to gene and protein expression measures of immune function and how they modify the gold standard biomarkers of disease and risk for AD and FTD in Latin America.

Conclusions

New opportunities for identifying novel diagnostic and therapeutic inroads may be easier to detect in Latin American populations that display a greater environmental and genomic diversity, while simultaneously elucidating potential strategies for reducing health disparities in Americans who face similar SDOH challenges.
Boston Remote Assessment for Neurocognitive Health in preclinical AD
Authors: Papp Kathryn V. , Amariglio Rebecca E.
Published: December 2022

Background

There is a need for cognitive assessments that can be completed remotely on personal devices which are sensitive to the earliest cognitive changes in AD. The Boston Remote Assessment for Neurocognitive Health (BRANCH) is a web‐based assessment including measures which tap into cognitive domains/processes known to decline early in the AD trajectory (e.g., associative memory, pattern separation). Tasks were designed to be intuitive and use stimuli relevant to everyday life. While BRANCH can characterize cognition at a single timepoint, learning curves (collected over 7 daily assessments) provide a unique cognitive variable that may to capture subtle but meaningful AD‐related memory decrements.

Methods

Participants completed three BRANCH tasks (memory for pairs of face‐names, grocery‐prices, and street signs‐digits) daily over 7 days (approximately 12 minutes/day) repeating the same stimuli to capture multi‐day‐learning‐curves (MDLC). Participants included 192 clinically normal older adults enrolled in the Harvard Aging Brain and related studies (mean age = 74.0, 63% female, 87% Caucasian, mean education = 16.6). Participants underwent PET imaging to assess global amyloid‐Aβ (PiB) and entorhinal cortex tau (FTP). Separate mixed models were used to determine whether differences in MDLC (composite performance across the 3 tasks) were associated with Aβ and tau.

Results

Controlling for age, sex and education, there was no association between amyloid and BRANCH performance on Day 1 (t = 1.07, p = 0.286). However, higher amyloid was associated with a diminished MDLC (t = ‐4.22, p<0.001; medium effect size between Aβ+/Aβ‐, Cohen’s d = 0.5). Higher entorhinal tau was similarly associated with diminished MDLC (t = ‐3.67, p<0.001); however, those with higher entorhinal tau also exhibited lower Day 1 performance (t = ‐1.99, p = 0.048).

Conclusions

Remote, digital testing provides the opportunity to deploy memory paradigms that mimic everyday life by exposing participants to repeated stimuli, such as the same face‐name pairs, over more frequent intervals. Results indicate that diminished MDLCs provide unique information about Aβ and tau‐related cognitive decrements, otherwise unable to be observed with a single timepoint (e.g., Day 1) assessment. We discuss how diminished MDLCs may serve as screening tool, a clinically meaningful outcomes over short timescales, and as a predictor for clinical progression.
REAL‐TIME AI‐BASED VOLUMETRIC ANALYSIS OF THE HIPPOCAMPUS IN PATIENTS WITH ALZHEIMER DISEASE
Authors: Salokhiddinov Marufjon , Stamou Elisabeth , Ismailova Munojat , Nuruddinov Ramziddin
Published: December 2022

Background

Patients suffering from a neurodegenerative condition such as Alzheimer's disease are more likely to experience hippocampal atrophy. Unfortunately, manually segmenting the hippocampus on a brain MRI scan is a time‐consuming procedure. Delineating the structure on several slices can consume a significant amount of radiologists' valuable time. We aim to use the real‐time AI method for hippocampal segmentation in patients with Alzheimer disease

Method

The study involved 65 participants in total, with a mean age of 72.65 5.35 years. The hippocampus volumes and asymmetry index (AI) were calculated using a 3D T1 isotropic sequence on United Imaging Healthcare 1.5 T scanner. Volumes were determined automatically using uAI‐Discovery Brain software. We used the T1‐3D sequence (voxel size [mm3]: 0.8 × 0.8 × 1; time [ms]: TE = 2.6; TR = 2000; TI = 900; duration [min]: 9:19) for manual and automatic segmentation of the hippocampus.

Result

The study revealed a high degree of concordance (ICC = 0.95) for both hippocampi. As a result, no major disparities existed between them. The subjects' mean right (2985.65344.25 mm3) and left (2898.69 225.2 mm3) volume was determined. These volumes and the asymmetry index were significantly different from those found in a sample of healthy participants (p = 0.00001 and p = 0.003, respectively), but were comparable to those obtained in a sample of subjects with AD

Conclusion

To emphasize, precise segmentation of the hippocampus via AI‐method can provide critical diagnostic information and open a new path in clinical settings
Development of Clinical Trial Simulation Tools for Alzheimer’s Disease through the Critical Path for Alzheimer’s Disease (CPAD) Consortium
Authors: Sivakumaran Sudhir , Cui Zihan , Priest Eileen , Lau Corissa , White Hazel , Irizarry Michael C , Romero Klaus , Karten Yashmin
Published: December 2022

Background

Critical Path Institute (C‐Path) coordinates the Critical Path for Alzheimer’s Disease (CPAD) Consortium. To accelerate DRUG DEVELOPMENT for Alzheimer’s Disease (AD), CPAD developed two regulatory‐endorsed clinical trial simulation (CTS) that sponsors can use to help optimize clinical trial design in 1) the pre‐dementia stages of AD, using CDR‐SB as the primary endpoint, and 2) mild‐to‐moderate AD, using ADAS‐cog as the primary cognitive endpoint. Recently, CPAD members have shared data from several contemporary Phase III clinical trials, offering an opportunity to enrich and expand these model‐based tools with additional fluid and imaging biomarker information, data from predementia subjects and treatment arms.

Method

By integrating patient‐level data from high quality Alzheimer’s disease (AD) clinical trials, models will be developed for multiple endpoints, and including demographics, time from and to diagnosis, genetic status (APOE4), and will be assessed using non‐linear mixed effects methods. Monte Carlo simulations will be performed to compare the statistical power by sample size in trials with and without enrichment using relevant covariates.

Result

As of January 2022, CPAD’s clinical trial repository contains 55 studies with 36,344 individual anonymized patient records. Analysis subsets generated from 6 key datasets, rich in fluid and imaging biomarkers, were used to develop of a preliminary set of disease progression models that characterize the time course of clinically relevant measures (ADAS‐Cog, CDR‐SB, other clinical assessment scales and biomarkers). A two‐level regression model was applied to predict baseline CDR‐SB using baseline covariates (demography, ApoE4 status, fluid and imaging biomarkers) and identify significant variables. Base models using parametric mixed‐effects approaches were developed with selection based on goodness‐of‐fit plots.

Conclusion

The disease progression models will serve as the basis for clinical trial simulation tools to facilitate informed decision making in the DRUG DEVELOPMENT process and optimize patient and endpoint selection, as well as design of efficacy studies. CPAD will advance the tools through the formal FDA Fit for Purpose pathway, to achieve regulatory endorsement and provide confidence to sponsors for the adoption of the tools.
Characterizing the relationship between telomere length and DNA methylation age in induced pluripotent stem cells during neuronal differentiation
Authors: Imm Jennifer L , Cope Emma L , Jones Kimberly M , Burrage Joe , Allen Nicholas D , Lunnon Katie
Published: December 2022

Background

Induced pluripotent stem cells (iPSCs) and their resultant neurons are popular models for studying diseases of aging, such as Alzheimer’s disease (AD). One hallmark of aging is the decreasing length of telomeres, the repetitive, protective DNA sequences at the end of each chromosome. We have previously demonstrated that whilst epigenetic age does increase with differentiation, iPSC‐derived neurons still have a fetal DNA methylation profile. It has also been shown by others that telomere length in iPSC‐derived neurons is shorter than the that of the stem cells from which they are derived. However, to our knowledge no one has looked at both epigenetic age and telomere length in the same samples. Therefore, we have collected DNA from different stages of the differentiation of iPSCs into neurons in order to look at the relationship between epigenetic age and telomere length.

Method

Human fibroblast cells were reprogrammed using lentiviral transfection. The resulting iPSC colonies were expanded, differentiated and collected at four different time points: day0 (iPSCs), day16 (neuronal progenitor cells), day37 and day58 (mature neurons). DNA methylation was assessed using the Illumina EPIC array and epigenetic age was derived using both the Horvath skin and blood clock and the Steg fetal brain clock. Absolute telomere length was determined using quantitative real‐time PCR.

Result

This study has identified the telomere dynamics of iPSCs as they undergo differentiation into cortical neurons. Not only this, but by also calculating the epigenetic age in the same samples we have been able to look at the relationship between telomere length and epigenetic age using two differentiation DNA methylation age calculators.

Conclusion

We have outlined the relationship between telomere length and DNA methylation age of iPSCs as they differentiate into cortical neurons. This information is important to consider when using iPSCs to model age‐related diseases such as AD.
The Effects of COVID‐19 on Australian Family Caregivers of People with Dementia: Caregiver COVID‐19 Limitations Scale.
Authors: Chen Maddysen , Thompson Claire L , Parkinson Lynne
Published: December 2022

Background

There is limited research on the effects of COVID‐19 and accompanying psychological and health related outcomes among Australian family caregivers. The aim of this research was to examine caregiver limitations as a result of COVID‐19, and measure this perceived impact on caregiving using the newly developed Caregiver COVID‐19 Limitations Scale (CCLS‐9). Psychometric properties of the CCLS‐9 were also examined.

Method

Forty‐four Australian family caregivers of individuals living with dementia completed a cross‐sectional online survey between May and September 2021. Outcome measures included psychological distress, caregiver burden, caregiver self‐efficacy, social support, quality of life, and COVID‐19 related caregiver limitations.

Result

Psychological distress and social support significantly predicted caregiver limitations. Australian family caregivers reported high levels of psychological distress and caregiver burden, low levels of self‐efficacy, moderate levels of perceived social support and quality of life. Overall COVID‐19 had a moderate impact on Australian family caregivers. The CCLS‐9 demonstrated good internal consistency and test‐retest reliability, poor concurrent validity, and results provided support for a two‐factor model of the CCLS‐9.

Conclusion

Findings from this study offer preliminary insight into the negative effects of COVID‐19 on Australian family caregivers. Distinctly, the pandemic continues to pose a significant threat to the health and psychological wellbeing of Australian family caregivers of individuals living with dementia. Therefore, Australian family caregivers should receive increased and ongoing support during these unprecedented times.
Declining Gait Speed is associated with Deteriorating Executive Performance in people with Mild Cognitive Impairment
Authors: Dolphin Helena , Fallon Aoife , McHale Cathy , Dookhy Joshi , Kennelly Sean P
Published: December 2022

Background

The Motoric Cognitive Risk Syndrome has highlighted the link between cognitive and motor performance, and the associated incremental higher risk of developing dementia. There is considerable debate regarding what aspects of cognition (working memory, executive function, attention) are most associated with gait changes. This study investigates the relationship between mobility scores and cognitive profiles in individuals with Mild Cognitive Impairment (MCI) specifically with regard to executive performance and amnestic/non‐amnestic profiles.

Method

Participants diagnosed with MCI, (Clinical Dementia Rating scale global score of ≤0.5, sum of boxes score ≤4.0), attending a regional specialist memory service had a three‐meter Timed Up and Go (TUG) gait assessment and multi‐domain neuropsychiatric assessment undertaken. Amnestic neuropsychiatric profile was defined as Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) delayed memory subset score <1SD i.e. ≤16th centile below norm for age/ education. Executive function performance was assessed using the Executive Interview (EXIT‐25) where higher scores reflect poorer executive performance.

Result

Data was reviewed for 161 patients with MCI; 53% (86/161) women. 80% (129/161) had an amnestic neuropsychiatric profile, mean age 73.8 ±7.2 (51‐94). 20% (32/161) had non‐amnestic MCI, mean age 74 ±7.07 (60‐87). There was no significant difference in TUG results between amnestic and non‐amnestic MCI patients (11.2 ±3.3 vs 10.7 ±3.1 p = NS). There was a significant increase in TUG values with worsening executive function performance [EXIT‐25 score 0–9 (88/161) mean TUG = 10.5 ±3.3 seconds vs EXIT‐25 score 10–14 (43/161) mean TUG = 11.9 ±2.8 seconds vs EXIT‐25 score 15–25 (30/161) mean TUG = 12.1 ±3.9 seconds; p = 0.021] which persisted after controlling for age, gender and other relevant cofactors.

Conclusion

Reflective of the importance of frontal lobe integration to the respective tasks, subtle differences in gait performance are associated with executive function performance regardless of predominant amnestic or non‐amnestic MCI profile.