bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebello‐Basal Ganglia Functional Connectivity Differences in Alzheimer’s Disease and Mild Cognitive Impairment
Authors: Gonzales Ivan Herrejon , Jackson T. Bryan , Hicks Tracey , Bernard Jessica A 
Published: January 2025

AbstractBackgroundExtensive research on the cerebral cortex and the hippocampus has improved our understanding of mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Historically, however, the cerebellum’s role in these stages of cognitive decline has been traditionally neglected due to its associations with motor function. Recent research has demonstrated cerebellar structural and connectivity differences in MCI and AD. Further investigating is however needed. In cognitively normal (CN) older adults cerebello‐basal ganglia (CB‐BG) functional connectivity is lower compared to younger adults. However, it remains an open question how these networks differ across different stages of cognitive decline and whether they are associated with cognitive and/or task performance.MethodHere, we investigated CB‐BG resting state networks associated with motor and cognitive cortical circuits across CN, MCI, and AD populations. The Alzheimer’s Disease Neuroimaging Initiative (ADNI‐3) was used to obtain the data of 478 participants who completed a motor and cognitive battery. All participants also underwent resting state functional magnetic resonance imaging (fcMRI). Analysis was completed using the CONN toolbox.ResultWe found a higher FC between Crus I with globus pallidus pars externa and lower FC between lobule VIIIb and dorsal caudal putamen in AD compared to CN individuals. However, no significant results were found when comparing AD to MCI or MCI to CN, suggesting that this stage of cognitive decline does not affect cerebello‐basal ganglia networksConclusionFurther understanding of network dysfunction that includes the cerebellum can help inform future clinical work and elucidate the mechanisms of MCI and AD.
Exploratory CSF proteomics biomarker outcomes of the the phase 2 clinical trial shine to assess the effects of CT1812 in Alzheimer’s patients
Authors: Caro Valentina Di , Lizama Britney N , Cho Eunah , Duong Duc M , Pandey Kiran , Blennow Kaj , Zetterberg Henrik , Levey Allan I. , Teunissen Charlotte , Caggiano Anthony O , Seyfried Nicholas T , Hamby Mary E. 
Published: January 2025

AbstractBackgroundSHINE (NCT03507790, COG0201) is a Phase 2 randomized, double‐blind, placebo‐controlled 6‐month trial, conducted to study the effect of the sigma‐2 receptor (S2R) modulator CT1812 in patients with Alzheimer’s disease (AD). An unbiased assessment of CSF proteomes from the patients that completed the SHINE trial was performed to identify pharmacodynamic (PD) biomarkers of target/pathway engagement and disease modification for CT1812.MethodTandem‐mass tag mass spectrometry (TMT‐MS) CSF proteomics was performed on baseline and end of study samples from an analysis of SHINE Part A and B to test the effects of two doses (100 mg, 300 mg; given orally, once daily) of CT1812 compared to placebo in mild to moderate AD patients. Change from baseline was calculated for each participant (N = 47), and differential abundance analysis (CT1812 vs placebo) was performed to assess treatment effects followed by Brain network mapping, Gene Ontology, and pathway analyses using STRING and Metacore (p≤0.1, p≤0.05). Pearson correlation analyses across levels of proteomic proteins and AD core biomarkers were also performed.ResultIn the interim analysis of the first 24 patients (SHINE‐A), differential expression analyses identified proteins altered (p≤0.1 and p≤0.05) in CT1812 vs placebo CSF, and hierarchical clustering demonstrated stratification of patients by treatment. Comparisons to reference standards showed proteins disrupted in or genetically linked to AD that were impacted by CT1812. Proteins dysregulated in AD were found to be normalized with CT1812 treatment (i.e., CLU) and biomarkers of pathway engagement were identified (i.e., APP, NPC1). Brain network mapping and pathway analysis identified statistically significant biological processes altered by CT1812, including those related to synapses, lipoprotein and amyloid beta biology, and neuroinflammation. Analyses of SHINE‐A and ‐B combined (N = 47) will be presented at this meeting.ConclusionCSF biomarker findings of the completed SHINE trial extend beyond that previously identified in the interim Part A analysis and shed light on potential biological proteins and/or pathways affected by CT1812. Pharmacodynamic biomarkers of CT1812 pathway engagement and disease modification were identified. Future investigation is warranted to determine if findings replicate in independent cohorts of AD patients.
Delivering Multidomain Lifestyle Intervention Via Telehealth: Findings from a Brain Health Program in the United States
Authors: Rao Anitha , Anderson Leyla , Wilkes Travis , Verdooner Steven R 
Published: January 2025

AbstractBackgroundMultidomain lifestyle interventions have been shown to improve cognition and functional status in adults at elevated risk of developing dementia. The delivery of lifestyle interventions has primarily occurred during face‐to‐face clinical encounters. Unfortunately, this limits patients who live in rural and underserved areas, as well as patients who have mobility issues and transportation difficulties.MethodA lifestyle curriculum was developed and delivered using telehealth. The study enrolled patients who met the criteria of a Mini‐Mental State Examination score >18 and could participate in the study through telehealth. Referrals primarily came from neurology and primary care clinics. An electronic medical record system was utilized to document progress and improvement. All participants shared their wearable technology data. A BrainHealth Educator (BHE) delivered personalized digital content to participants, focusing on exercise, nutrition, and sleep. The content was tailored to each participant’s risk factors, APoE genotype, and communication preferences.ResultThe study included 30 participants, with 23 females and 7 males ranging in age from 40 to over 70 years old. The enrollment and completion rates for exercise programs was 83%, for sleep programs was 83%, for nutrition programs was 58%, with an updated module currently being tested. The average duration of BHE telehealth visits was 30 minutes. There was high acceptance and satisfaction with communicating APOE test results via telehealth. 75% of participants actively used the app and 25% used the phone. 50% of patients logged in once per week. The study covered 9 geographic divisions across the US, achieving engagement across diverse practices, clinicians, and socioeconomic backgrounds, including neurologists, primary care physicians, and geriatricians. 75% of patients provided wearable data, with continuous wearable data submissions. The attrition rate was <10%.ConclusionThis study successfully demonstrates that lifestyle intervention delivered via telehealth by a BHE resulted in high patient engagement and satisfaction at nationwide scale. As cognitive health assessment and management rapidly develops, there is a need for lifestyle intervention programs that are structured to support patients at all stages and eliminate health disparities.
Improving the Chance of Success for Alzheimer’s Clinical Trials by Identifying and Mitigating the Risk of Fraudulent Practices
Authors: Hendrix Suzanne B. , O'Keefe Patrick P , Zhang Jeffery , Hendrix Kent , Wang Lixia , Dickson Samuel P. 
Published: January 2025

AbstractBackgroundCompanies recently identified clinical study sites engaging in fraudulent practices, reducing success in Alzheimer’s disease (AD) clinical trials. Successful trials are reliable despite possible victimization by these practices because these sites introduce a negative bias. Ease of simulating Alzheimer’s diagnosis documentation (based on clinical or blood markers) and clinical outcome data, coupled with inadequate oversight by Contract Research Organizations (CROs), facilitates deceptive practices.Fraudulent practices at sites and with patients (“professional patients”) often go hand‐in‐hand and flourished during COVID. These must be aggressively addressed in the post‐COVID environment. Requiring and scrutinizing PET scans increases the chance of detecting fraud. Alarmingly, sites most prone to deceitful practices include predominantly underrepresented populations, thwarting inclusion efforts.MethodWe reviewed completed and ongoing studies to estimate the percentage of potentially fraudulent sites. We developed medical audit methods to identify issues invisible in regulatory audits. Traditional data management and statistical analysis methods fail to identify these issues. We use expected enrollment and true effect size to estimate potential bias and added variability introduced by these sites. We propose methods for detecting fraud based on clinical and operational data.ResultIn studies not requiring PET scans, approximately 10% of sites may be fraudulent, corresponding to a higher proportion of enrolled subjects (∼20‐30%). These sites can reduce observed effect size by 40% (estimated bias) at best and can completely cancel out a true treatment effect at worst. We estimate variability increases by 35‐100%, reducing our ability to observe significance. Algorithms to identify fraudulent sites will be gladly shared confidentially, but not broadly, to prevent sites from circumventing our algorithms.ConclusionAD clinical trials affected by even a minority of fraudulent sites may have underestimated treatment effects. We developed a toolbox for combating these issues. It includes best practices for enhanced CRO oversight, incorporation of medical expertise in audits, and identification of problems based on targeted, blinded statistical algorithms. We freely share it with qualified researchers. Awareness of and taking an aggressive stance as a community against these fraudulent practices can safeguard AD research integrity, protect and benefit vulnerable populations, and accelerate development of effective therapeutics.
Mapping lipids associated with Aβ plaques in a mouse model of Alzheimer’s disease via multiscale mass spectrometry imaging
Authors: Trinklein Timothy , Rubakhin Stanislav S. , Asadian Marisa , Sabitha K.R. , Lazarov Orly , Lam Fan , Sweedler Jonathan V 
Published: January 2025

AbstractBackgroundIncreasing evidence shows that many lipids play important roles in the pathogenesis of Alzheimer’s disease (AD), including Aβ plaque formation. Of note, the greatest genetic risk of late onset AD, apolipoprotien E4 (APOE4), plays a major role in lipid transport. However, the profile of lipids that play a role in AD is poorly understood. Mass spectrometry imaging (MSI) is a tool of choice for quantifying and spatially mapping lipids in biological samples. Here, we apply MSI at the tissue‐ and single cell‐level to profile lipids in the brains of 5xFAD and wild type mice to identify lipids associated with Aβ plaques.MethodFemale 5xFAD mice at 5 months of age (n = 3) and age‐ and sex‐matched wild type (n = 3) were used. After sacrifice, brains were removed and a coronal slice was frozen and used to obtain 12 µm tissue sections. Fresh tissue was dissected, dissociated into single cells, and dispersed onto glass slides. Using matrix assisted laser desorption ionization (MALDI) MSI, we imaged tissue slices (n = 12, two per animal) and over 10,000 individual cells. After MSI, sections were stained with Thioflavin S and imaged by epifluorescence microscopy. Statistically significant lipids between classes were discovered by the Wilcoxen rank‐sum test with Benjamini‐Hochberg correction.ResultCo‐registration of mass spectrometry imaging data with histological staining allowed us to identify a suite of plaque‐colocalized and depleted lipids (Fig. 1). We found that many lipid classes including monogangliosides (GM), hexosylceramids (HexCer), phosphatidic acids (PA), phosphatidylethanolamines (PE), phosphatidyleinositol (PI), and lysophosphatidylecholines (LPC) were plaque‐colocalized and in higher abundance in 5xFAD animals relative to controls (Fig. 2). In contrast, sulfatides (ST) were depleted in plaques and in lower abundance (Fig. 2). In total, we identified 20 plaque‐enriched lipids and 5 plaque‐depleted lipids. All 25 lipids were detected in single cells, recapitulating the trends shown in tissue‐level data (Fig. 3).ConclusionOur finding revealed accumulation and depletion of lipids in the plaque microenvironment and single cells. Work is ongoing to extend our approach to different ages (to observe disease progression) and other models, such as APOE3/4 knock‐in animals.
Lifestyle Factors’ Influence on Episodic Memory: A Gradient Boosted Tree Analysis
Authors: Berg Addison , Sinclair Stephanie , Acosta‐Parra Ashley , Glosson Ana Nazmi , Moreno Cesar , Fletcher Evan 
Published: January 2025

AbstractBackgroundComprehending the role of participatory lifestyle factors influencing the aging process and subsequent cognitive outcomes is imperative for postulating ways to combat cognitive decline. Recent research points to the independent impacts of leisure time activities (LTAs), physical performance (measures of physical fitness) and socialization (relationships and interaction frequency) on healthy cognitive aging, although the relative importance of this triad of factors is poorly delineated.MethodFrom baseline data of two studies examining cognitive aging in older, diverse populations— “Study of Healthy Aging in African Americans” and “Kaiser Healthy Aging and Diverse Life Experiences,” we scraped subjects’ self‐reported data and Spanish and English Neuropsychological Assessment Scales (SENAS) measured cognitive performance scores. Lifestyle survey questions revealed features that well‐represented each category in the triad. These features were used as model inputs, along with sex, education, and income. The cohort consisted of n = 1684 subjects, each characterized by 23 features, after removal for missingness. We applied a grid search algorithm with 5‐fold cross‐validation to tune the hyperparameters of a gradient boosted decision tree model. Optimized for accuracy and generalizability, these parameters defined the model to predict episodic memory scores. Per prediction, relative feature importances were computed as Shapley values. Mean absolute importances (global importance) for the full cohort were derived from the relative values. For triad comparison, summated global importance of the features for each lifestyle category was calculated.ResultGroup importance ranking revealed aggregated LTAs with the largest contribution to episodic scores, followed by physical performance, then socialization. Notable LTAs included complex cooking, taking classes, and gaming. Although no individual mean absolute feature importance surpassed that of sex, the aggregate importance of the LTA and physical performance groups did; all categories exceeded education and income.ConclusionOur major finding indicates that, beyond the typical factors of interest for episodic memory and healthy cognitive aging, the way one spends their free‐time has a strong association with these outcomes, and suggests LTAs are the most important. It’s worth noting that these three domains may overlap (ex. recreational sporting activities). This research may influence public health guidelines for promoting healthy cognitive aging.
Increased cerebral blood flow after lecanemab infusions: MR‐ASL utility in monitoring Alzheimer disease treatment response
Authors: Nordvig Anna S , Fajardo Andres Ricaurte , Chiang Gloria 
Published: January 2025

AbstractBackgroundSince lecanemab, an anti‐amyloid monoclonal antibody targeting Aβ protofibrils, only modestly impacts cognition (27% slower cognitive decline over 18 months), tracking the effects on the brain in the early months is a clinical challenge. Serial noncontrast MRI scans are required by the FDA, to assess for the occurrence of amyloid‐related imaging abnormalities (ARIA). Arterial spin‐labeling MR (ASL‐MR) is a 4‐minute non‐contrast easily‐added sequence. Patterns of abnormal cerebral blood flow (CBF) on ASL‐MR can correlate with neurodegenerative markers including FDG‐PET.MethodHere we show CBF maps of two patients at baseline, and after receiving 4 infusions of lecanemab. Our figure is representative of six other patients in whom we have noted similar changes on therapy, and who will also be presented.ResultFigure 1 shows CBF maps of a man in his early seventies with mild cognitive impairment, due to AD. He had a family history of AD, and was diagnosed with a positive 18F‐florbetaben PET and prescribed donepezil, with mild symptom improvement. His CSF markers were borderline (Abeta42 575 pg/mL, t‐tau 289 pg/mL, p‐tau 51 pg/mL, ATI 0.99.). Figure 2 shows CBF maps of a woman in her fifties, with a history of Crohn’s disease, not currently requiring immunosuppression. She was diagnosed with posterior cortical atrophy due to AD, with a positive 18F‐florbetaben PET and CSF compatible with AD (abeta42 366 pg/mL, t‐tau 486 pg/mL, p‐tau 72 pg/mL, ATI 0.45). She remained employed until a mild COVID infection, at which point her preexisting cognitive symptoms worsened (presumed longCOVID‐related worsening). Both patients carried the ApoE e3/e3 genotype. In both cases, baseline low temporoparietal CBF increased at the scheduled MRI post‐4th infusion.ConclusionThese cases show that CBF increases on lecanemab from baseline to after the 4th infusion. Preclinical investigations have demonstrated that it can protect neurons from Aβ‐induced apoptosis, leading to neuronal viability and improved brain perfusion. CBF increases may also reflect increased synaptic activity after amyloid clearance and/or vascular changes, such as clearance of fibrinogen/amyloid clotting complexes. CBF has potential as a noninvasive and time‐efficient marker of medication effect and perhaps efficacy over time.
ChristianaCare Swank Memory Center: Launching GUIDE as a New Model Program
Authors: Huege Steven F 
Published: January 2025

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Noval Selective Ligand‐Extraction of Bioactive Components in Complex Natural Products Applying Immobilized Multi‐Target Magnetic Beads
Authors: Wang Chen , Qin Xueying , Wang Ying , Wang Weiping , Sun Shuai , Wang Hongsen , Li Shiyu , Dai Xiao , Zhu Xianhong , Gao Xun , Qin Kunming , Zhang Qing 
Published: January 2025

ABSTRACTChoerospondias axillaris is a medicinal plant used for treating coronary heart disease (CHD) due to its broad spectrum of anti‐inflammatory activities. Cyclooxygenase 2 (COX‐2) and lipoxygenase 5 (5‐LOX) were immobilized on magnetic nanoparticles for selective ligand‐extraction of these two enzymes present in C. axillaris. Sixteen extracted components were identified and analyzed using ultraperformance liquid chromatography plus Q‐Exactive Orbitrap tandem mass spectrometry (UHPLC‐Q‐ExactiveOrbitrap‐MS/MS), including flavonoids Curcumin and Epicatechin. The metabolization of the aforementioned 16 components in rats with acute blood stasis indicated a solid pharmacodynamic foundation. This method offers an effective approach for conducting basic research on the enrichment, analysis, and efficacy evaluation of active components in complex natural products.
Can Sustainability Pay Off? Evaluating ESG Disclosure and Financial Outcomes in Chinese's Health Care Firms
Authors: Dossa Joel Victor 
Published: January 2025

ABSTRACTThis study analyzes the influence of environmental, social, and governance disclosure (ESG) on the financial performance (FP) of health care firms listed in Shanghai and Shenzhen Stock Exchange Markets in China. Based on both stakeholder and signaling theory, using panel data from 2012 to 2022 Ordinary Least Squares (OLS) and System Generalized Method of Moments (GMM), we investigate the influence of ESG overall disclosure score together with their individual components (environmental, social, and governance) on the FP of health care firms. We find that ESG activities have a significant positive impact on the company's both accounting and market‐based measures of performance. In addition, governance and social activities have a positive significant effect on FP. However, environmental activities and disclosure were negatively and significantly associated with FP. The study provides novel insights by describing the nuanced financial trade‐offs of ESG practices in a highly regulated and capital‐intensive industry like health care. It contributes to the literature by emphasizing that although environmental investments may hinder short‐term FP, strong governance and social activities remain essential drivers of sustainable performance in health care. The study provides empirical insights on how ESG practices impact FP in the health care industry and complements the available literature on the economic efficiency of ESG performance, particularly in FP. This calls for more refined ESG strategies tailored to sector‐specific realities.
WDANet: Exploring Stylized Animation via Diffusion Model for Woodcut‐Style Design
Authors: Ou Yangchunxue , Xu Jingjun 
Published: January 2025

ABSTRACTStylized animation strives for innovation and bold visual creativity. Integrating the inherent strong visual impact and color contrast of woodcut style into such animations is both appealing and challenging, especially during the design phase. Traditional woodcut methods, hand‐drawing, and previous computer‐aided techniques face challenges such as dwindling design inspiration, lengthy production times, and complex adjustment procedures. To address these issues, we propose a novel network framework, the Woodcut‐style Design Assistant Network (WDANet). Our research is the first to use diffusion models to streamline the woodcut‐style design process. We curate the Woodcut‐62 dataset, which features works from 62 renowned historical artists, to train WDANet in capturing and learning the aesthetic nuances of woodcut prints. WDANet, based on the denoising U‐Net, effectively decouples content and style features. It allows users to input or slightly modify a text description to quickly generate accurate, high‐quality woodcut‐style designs, saving time and offering flexibility. Quantitative and qualitative analyses, along with user studies, confirm that WDANet outperforms current state‐of‐the‐art methods in generating woodcut‐style images, demonstrating its value as a design aid.
High performance CO reduction at electrolyzer stack level through system optimization
Authors: Ayyub Mohd Monis , Fődi Tamás , Endrődi Balázs , Janáky Csaba 
Published: January 2025

AbstractThis study demonstrates the electrochemical reduction of carbon monoxide (COR) at high current densities in a zero‐gap electrolyzer cell and cell stack. By systematically optimizing both the commercially available membrane electrode assembly components (including binder content and gas diffusion layer) and the operating conditions, we could perform COR at current densities up to 1.4 A cm−2 with a maximum C2+ selectivity of 90%. We demonstrated the scale‐up to a 3 × 100 cm2 electrolyzer stack that can sustain stable operation at 1 A cm−2 for several hours without significant performance decay and with a total C2+ selectivity of ~80% and an ethylene selectivity of ~40%. We provide critical insights into the holistic optimization of key system parameters, without using special catalysts or surface additives, which can pave the way for scalable and industrially viable COR processes.