bluuebunny/crossref_metadata_2025_split huggingface dataset:
Commercial Copper‐Catalyzed Aerobic Oxidative Synthesis of 4H‐3,1‐Benzoxazine and Their Effects on Anti‐Inflammatory Genes Expression
Authors: Jongcharoenkamol Jira , Saewa Rujiporn , Intasri Atchariya , Atawong Pariya , Changtor Phanupong , Buddhachat Kittisak , Kerdphon Sutthichat 
Published: January 2025

AbstractA facile green synthesis of the anti‐inflammatory gene expression of 4H‐3,1‐benzoxazine was developed under a commercial copper catalytic system. Benzoxazines were synthesized from 2‐aminobenzyl alcohols and aromatic aldehydes including heterocyclic aromatic aldehydes using an economical commercially available copper(I)iodide (CuI) as a catalyst in the presence of the base, tBuOK. Target products were achieved in moderate to high yields with up to 75 % isolated yield. 4H‐3,1‐Benzoxazine enabled down‐regulation of inflammatory gene expression including tumor necrosis factor‐α (TNF‐α), inducible nitric oxide synthase (iNOS), cyclooxygenase‐2 (COX‐2), and interleukin‐1β (IL‐1β) in the lipopolysaccharide (LPS)‐stimulated RAW 264.7 macrophage cell line using a real‐time quantitative polymerase chain reaction (RT‐qPCR) comparable to anti‐inflammatory drug, dexamethasone. These results demonstrated that 4H‐3,1‐Benzoxazines possess the potential capability of anti‐inflammation.
Visible‐Light‐Induced Carbopyridylation of Maleimides with Pyridine Salts Under Catalyst‐Free Conditions
Authors: Ma Zijia , Wang He , Li Chunbo , Liu Ningning , Wang Yujia , Sun Jing , Wang Xin , Sun Ran , Li Lei 
Published: January 2025

AbstractA catalyst‐free carbopyridylation reaction of maleimides with N‐benzoylmethylpyridinium bromides under visible light irradiation is reported. The carbo‐2‐pyridylation products of maleimides are obtained in good yields, demonstrating broad substrate scope and high functional group tolerance even on a gram scale. Mechanistic studies suggest that the process involves a tandem [3+2] cycloaddition, and Norrish‐type‐II fragmentation.
Stone Tool Use by Black‐Horned Capuchin Monkeys (Sapajus nigritus cucullatus) in an Urban Park in Londrina, Brazil
Authors: Gutierres Julia Santos , Pereira Felipe Santos Machado , Lynch Jessica Ward , Vidotto Magnoni Ana Paula 
Published: January 2025

ABSTRACTTool use to crack open palm nuts has been observed extensively in some capuchin monkey species. However, for southern black‐horned capuchin monkeys (Sapajus nigritus cucullatus), there is only one published record of stone tool use from the 1990s, from an urban park in Londrina, Brazil. In the present study, we returned to this urban park to systematically investigate the hammer‐and‐anvil sites used to crack nuts by this capuchin monkey population. We analyzed the fruit and shell remnants resulting from hammering to test the following hypotheses: (1) hammers at tool‐use sites are actively chosen for size and/or weight, (2) tool use sites that are closer to a tree of the processed plant species are more frequently used, and (3) there is no seasonal effect modulating hammer‐and‐anvil use for processing nuts. We located and identified 205 tool‐use sites through active search within the park, and we measured and weighed the tools involved in hammering activity. We compared hammer weight and size to that of the comparable material available in the environment and found that hammer size and weight differed significantly from that of the raw materials found in the environment, suggesting active choice of the hammers. We identified three plant species for which nuts were processed through tool use: Syagrus romanzoffiana, Acrocomia aculeata and Terminalia catappa. Through measuring the distance between each tool‐use site and the nearest tree of the plant species processed there, we found that closer proximity between the tool‐use site and the nearest target tree (Syagrus and Acrocomia) increased cracking frequency. We returned to each site three times during the study year to determine if new tool use activity had occurred, and our data indicate habitual use of tools to crack open nuts throughout the year, with no large differences between seasons.
Gait and cognitive function in the elderly with AD dementia, MCI and healthy
Authors: Moon Seok Woo 
Published: January 2025

AbstractBackgroundThe purpose of this study was to compare gait pattern and cognitive function among elderly patients with Alzheimer’s Disease (AD), elderly people with Mild Cognitive Impairment (MCI), and Healthy Controls (HC).MethodTwenty three elderly patients participated: 25 AD (78.4±6.37 yrs), 25 MCI (74.9±6.31 yrs), and 30 HC (73.8±5.45 yrs). Gait and Cognitive function were collected using an accelerometer attached to the foot and the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease (CREAD‐K), respectively. To compare differences in gait performance among groups, mean stride time, magnitude and structure of gait variability and ratio of low frequency and high frequency (LF/HF ratio) of stride time sequence were used in this study.ResultResults showed that gait variables (mean stride time, LF/HF ratio of stride time) were useful for classification between MCI and HC. Cognitive function tests (J1, J3, J4, J6, and J8 of CREAD‐K) represented the difference between AD and HC.ConclusionThis study may provide a foundation for future work on progression of dementia.
Use of Technology to Remotely Assess Language as a Non‐Invasive Biomarker: The Importance of Language Task
Authors: Saylor Anna K , Cohen Matthew L. , MacWhinney Brian , Fromm Davida , Stagge Faith , Lanzi Alyssa M 
Published: January 2025

AbstractBackgroundThere is growing evidence that discourse (i.e., connected speech) could serve as a cost‐effective and ecologically valid means of identifying individuals with prodromal Alzheimer’s disease. Specifically, metrics of semantic content appear to be sensitive to early mild cognitive impairment (MCI; Mueller, Koscik, Clark et al., 2018). These results were from spoken discourse samples from a brief, decontextualized picture description task (i.e., “Cookie Theft”) that may have task‐specific language demands. This study aims to determine if discourse produced from other task types elicits different levels of semantic content.MethodDiscourse data were taken from the Delaware Corpus in DementiaBank, an open‐access online database of multimedia interactions (Lanzi et al., 2023). Participants’ cognitive status was documented in the database: cognitively healthy (n = 24) or MCI (n = 43) based on NIA‐AA and Petersen’s (2011) criteria. Using Zoom, participants completed six spoken discourse tasks including picture description (“Cookie Theft”), story narrative (“Cat Rescue”, “Rockwell”, “Cinderella”), procedural discourse (“PBJ”), and personal narrative (“Hometown”). Discourse samples were transcribed using an automatic speech recognition (ASR) pipeline and analyzed using CLAN software (Liu et al., 2023). Semantic content was measured by three variables: percent nouns, percent verbs, and pronoun index (Mueller, Koscik, Hermann et al., 2018).ResultInteraction effects of cognitive status by task were evaluated for each semantic variable. Two‐way ANOVAs yielded non‐significant interaction effects (p>0.05). Therefore, we aggregated our task data across cognitive status to conduct one‐way ANOVAs. Each semantic variable ANOVA produced a main effect of task: F%noun(5, 394) = 30.63; F%verb(5, 391) = 31.64; Fpronoun(5, 391) = 23.68, all p values<.001 (see figures). Post‐hoc comparisons revealed that the highest level of each semantic variable was produced by a different discourse task (e.g., PBJ = highest percent nouns).ConclusionThis discourse study was efficiently executed with the use of remote data collection, an ASR transcription pipeline, and CLAN for analysis. Each discourse task elicited differing levels of semantic content. As efforts continue to study language as a non‐invasive biomarker for cognitive decline, researchers should consider which discourse task(s) would best support their aims.
Cognitive dynamics in preclinical and very mild Alzheimer disease
Authors: Aschenbrenner Andrew J. , Welhaf Matthew S. , Hassenstab Jason J. , Jackson Joshua J. 
Published: January 2025

AbstractThe widespread use of remote digital assessment technology has made it possible to obtain high‐frequency measurements of cognitive function in naturalistic settings (i.e., outside of the clinic). Measurement burst designs feature multiple waves of testing (e.g., multiple tests per day for several weeks) which are repeated at regular intervals (e.g., annually) and have been shown to be feasible, well‐tolerated by participants, and provide substantially more reliable estimates of mean performance than standard assessments. Measurement burst designs also afford an examination of cognitive variability, or the degree to which cognitive scores vary across repeated assessments. Variability can be measured at different time scales including momentary variability across trials within a task, or over different days. Measures of “contextual factors” such as perceived stress, sleep quality, mood, and personality traits are easy to add as well to test potential mechanisms for differences in cognitive variability. An integration of cognitive and contextual variability across multiple time scales provides a more complete picture of change in early‐stage disease and is particularly applicable to preclinical Alzheimer disease (AD) where cognitive declines are extremely subtle and heterogeneous.Using data from two high‐frequency assessment studies in which cognitively healthy and very mildly impaired older adults completed multiple daily cognitive assessments of episodic memory, working memory, attention, and processing speed for 1 to 3 weeks, we will examine how variability at both short (from trial to trial within a task) and longer (from day to day) timescales change as a function of preclinical AD. We examine potential mechanisms for cognitive variability including increased mind wandering, daily motivation, and variations in daily personality traits. Finally, we will discuss the utility of advanced statistical modeling techniques (e.g., mixed effects location scale models) to answer questions about cognitive variability, and we will examine how our understanding might be further enhanced by employing cognitive process models (such as the diffusion model) that incorporate both accuracy and response time to provide a more complete picture of daily cognitive fluctuations in AD. We end with practical considerations regarding administration of measurement bursts and pose additional questions that will stimulate additional research.
Multiple sclerosis and legal capacity
Authors: Voskou Panagiota 
Published: January 2025

AbstractBackgroundCognitive deficits may occur in about 60% of patients with multiple sclerosis (MS) and executive functions, working memory and new‐learning are commonly impaired. Nevertheless, there is limited research regarding decisional capacity in MS. Financial and treatment‐decision capacity are complex activities of daily living.MethodA literature review in the Pubmed database has been made, using the keywords: multiple sclerosis, legal capacity, decision‐making.ResultOverall financial capacity (FC) and more complex financial domains, i.e. managing bank accounts, are significantly impaired in progressive MS, with mental flexibility and working memory mostly involved. Short‐term verbal memory and basic arithmetic ability are found to be major neurocognitive predictors of FC in progressive MS. Ability to understand treatment and clinical research is commonly impaired in MS, i.e. misunderstanding treatment details due to diminished new‐learning or executive functions or difficulty comprehending treatment risks and benefits. Recognition cueing is found to be helpful for robust informed consent from MS patients. Depressive distress is also common in MS and this corresponds with poor reasoning and, subsequently, decisional incapacity.ConclusionMore studies should be conducted about the capacity for informed consent and financial tasks in MS, as well as which neurocognitive functions are related to specific components of medical decision‐making. The primary goal should be the protection of rights and autonomy in MS. Depression and its neurocognitive correlates in MS should be also examined in future research.
Early memory loss and financial capacity A “Real World” Assessment
Authors: Lichtenberg Peter A 
Published: January 2025

AbstractBackgroundAssessing financial capacity in older adults with memory loss is becoming an increasingly important area so as to minimize wealth loss and cases of financial exploitation. The National Academy of Sciences has recommended “real world” assessment of financial management and yet this continues to be lacking. The WALLET (Wealth Accumulation and Losses in Late‐life Early Cognitive Transitions) study provides a new “real world” approach to assessing financial management.Method150 older adults, approximately half with early memory loss and half without, provided 12 months of their checking account statements. These were reviewed for key indicators and then interviews were conducted to insure the older person was the primary manager of the account, to establish annual income and document inflows and outflows. Measures of financial decision‐making, financial literacy, numeracy, memory functioning and indicators for a new Financial Vulnerability Index were collected. Bivariate and multivariate analyses were used to predict excess spending.ResultParticipants with early memory loss reported significantly lower IADL functioning, had lower memory scores (RAVLT), higher financial decision‐making vulnerability scores and higher excess spending than did those with no memory loss. The association between cognitive status and excess spending was explained by adjustment for the financial decision‐making tool (LFDRS) and the new Financial Vulnerability Index (FVI).ConclusionReal world assessment of financial functioning in older adults with early memory loss can assist in identifying deficits in financial management. A new method for this assessment was established.
The Relationship Between Insight and Anxiety Within a Diverse Alzheimer’s Disease Sample
Authors: Heald Jewel , Forgeard Marie , Osher Jason 
Published: January 2025

AbstractBackgroundA growing number of individuals and families are affected by Alzheimer’s disease (AD) across the United States. Changes in insight and levels of anxiety have been extensively but independently investigated in this population. In contrast, research on the relationship between insight and anxiety has been limited and has yielded inconsistent results.MethodThe present study used the NACC Uniform Dataset (N = 18,671) to examine cross‐sectional associations between insight and anxiety in a diverse AD sample in order to better understand their potential role in individuals’ presenting symptoms and overall distress.ResultResults showed that although higher insight was associated with higher anxiety, this effect disappeared when controlling for other variables. Instead, age of onset, disease severity, and depression severity emerged as significant predictors of greater anxiety. In addition, depressive symptoms also moderated the relationship between insight and anxiety. For participants with lower depression, high insight was associated with lower anxiety. Results also supported the notion that race/ethnicity may play a role in the relationship between insight and anxiety. Overall, Black/African American participants in this study had somewhat lower levels of anxiety than other participants. In addition, within participants with low insight only, Hispanic/Latino/a/x participants had higher levels of anxiety than others.ConclusionThese findings provide valuable insight into the emotional experiences of patients with AD and may help inform clinicians about potential treatment and intervention options.
The interplay of cognitive and motor impairment in the occurrence of dementia and presence of brain pathologies: a community‐based cohort study
Authors: Wang Jiao , Welmer Anna‐Karin , Bennett David A. , Xu Weili 
Published: January 2025

AbstractBackgroundEvidence on the additive effect of mild cognitive impairment (MCI) and motor function (MF) impairment on dementia and brain pathologies is sparse. We aimed to explore the incidence of dementia including Alzheimer’s dementia, and brain pathologies among people with both MCI and low MF.MethodsWithin the Rush Memory and Aging Project, 1,814 dementia‐free participants (mean age: 79.7±7.4 years; 74.4% female) were identified at baseline and followed up to 24 years to detect incident dementia. Baseline motor function was assessed by a composite score of dexterity, gait, and hand strength, and tertiled (low, moderate, and high). MCI was defined as the presence of cognitive impairment but not meeting criteria for dementia. Then, four groups were classified: (I) normal, (II) isolated low MF, (III) isolated MCI, and (IV) MCI & low MF. Dementia including Alzheimer’s dementia was diagnosed following international criteria. During the follow‐up, 850 participants died and underwent autopsies for neuropathological assessment (including Alzheimer’s disease, vascular, and other brain pathologies). Data were analyzed using Cox regression and logistic regression.ResultsAt baseline, 964, 380, 245, and 225 participants were in the above four groups, respectively. During the follow‐up (median [interquartile range]: 6 [3‐9] years), 506 (27.89%) participants developed dementia, including 469 (25.85%) Alzheimer’s dementia. Compared to the normal group, the multivariable‐adjusted hazard ratios (95% confidence intervals) of MCI & low MF was 5.65 (4.26‐7.50) for dementia and 5.78 (4.31‐7.76) for Alzheimer’s dementia. A significant additive interaction was found between MCI and low MF on dementia risk (AP 0.49: 0.31‐0.66). In the brain pathological data analysis, MCI & low MF was significantly related to higher neurofibrillary tangles (odds ratio 1.99: 1.25‐3.16), cerebral atherosclerosis (2.40: 1.39‐4.12), Lewy bodies (1.71: 1.01‐2.90), and hippocampal sclerosis (3.50: 1.56‐7.86), compared to the normal group.ConclusionAdding MF to the assessment of MCI could better detect dementia risk. Both neurodegenerative and vascular mechanisms may underlie the interplay between MF and MCI.
LncRNA Gm20063 alleviates cognitive impairment in APPswe/PS1dE9 mice
Authors: Zhu Xiaolei , Lan Zhen , Xu Yun 
Published: January 2025

AbstractBackgroundCompelling evidence has shown that long non‐coding RNAs (lncRNAs) contribute to Alzheimer’s disease (AD) pathogenesis including β‐amyloid plaque deposition (Aβ) and intracellular neurofibrillary tangles. In this study, we aimed to investigate the critical role of lncRNA Gm20063 in AD.MethodSix‐month‐old male APP/PS1 transgenic mice and wild type (WT) C57BL/6 (B6) littermates were obtained from the Nanjing University Animal Model Research Center. AAV mediated over‐expression or knockdown of Gm20063 in hippocampus neurons though stereotactic technique. Behavioral tests were performed to evaluate the cognitive and memory function of APP/PS1. Electrophysiological tests, Golgi staining and Western blotting was applied to determine the synaptic plasticity. The potential targets of Gm20063 were identified by mass spectrometry (MS), RNA‐binding protein immunoprecipitation (RIP) and RNA in situ hybridization (RNA scope).ResultThe expression of Gm20063 was significantly increased in the hippocampus of APP/PS1 mice. Overexpression of Gm20063 ameliorated cognitive decline, reduced Aβ deposition, enhanced synaptic plasticity and Aβ phagocytized by microglia in APP/PS1. In addition, knockdown of Gm20063 accelerated the memory deficits and worsened the AD pahogenesis in APP/PS1 mice. Furthermore, Gm20063 interacted with TDP‐43 in the hippocampus, and regulated the post‐translational modifications of TDP‐43.ConclusionGm20063 attenuated cognitive decline in AD mice, and targeting Gm20063 might be an effective therapy for AD treatment.
The Utility of Study Insight Analytics (SIA) Algorithms in Identifying Scoring Error Risks in the Clinical Dementia Rating scale (CDR)
Authors: Negash Selam , Echevarria Barbara , Blattner Raymond , Randolph Christopher 
Published: January 2025

AbstractBackgroundClinical trials in Alzheimer’s Disease (AD) suffer from high failure rates, in part due to imprecision in endpoint measurements that introduces noise1. SIA is a quantitative approach that utilizes algorithms to identify inconsistencies in measurements that may be indicative of problematic scale administration and/or scoring errors. The CDR, a sole primary and key secondary endpoint in many AD trials, can be challenging to score, particularly in early symptomatic and mild diseases2. The goal of this study was to develop and validate SIA algorithms for CDR, and to evaluate their incidence and association with scoring errors.MethodsAggregated data from 40,148 CDR reviewed assessments across 34 multinational trials of pre‐clinical, early symptomatic, and mild to moderate dementia due to AD were analyzed. Algorithms indicative of scoring errors on the basis of clinical judgement were developed. These were then subjected to a validation procedure to determine both the rates flag trigger, and the degree to which each flag was associated with increased scoring errors. The development and validation of one of these flags (the cognitive‐functional difference score)3 is described in detail as an example. Algorithms that fire relatively infrequently (to minimize false positives), independently (indicating increased probability of scoring errors), and associated with increased error rates were identified.ResultsFive flags emerged from the validation process to meet criteria of relatively low firing rate (<10%), association with increased rates of scoring errors, and having relatively orthogonal relationships with each other. The latter goal was established by a strong linear relationship between number of flags triggered and scoring error rate, such that as the number of flags triggered increased, the mean error rate was significantly elevated (estimate = 0.20, SE = 0.008; p < 0.0001).ConclusionThe present study, using a large, aggregated dataset across multiple AD trials, demonstrated the utility of SIA algorithms in detecting data inconsistencies that help identify problematic assessments in CDR. The very strong association between flags triggered and error rates suggests that the algorithms can serve as a proxy for identifying assessments that are predictive of scoring errors and to surface these assessments for review/remediation.