bluuebunny/crossref_metadata_2025 huggingface dataset:
Multicolor Fine‐Tunable Upconversion Luminescence from a Single Nanoparticle for Full‐Color Displays with a Wide Color Gamut
Authors: Shin Seungyong , Lim Jun Pyo , Hong Yun‐Kun , Kyhm Jihoon , Hong A‐Ra , Kang Gumin , Ko Hyungduk , Oh Soong Ju , Jang Ho Seong
Published: January 2025

Recently, upconversion nanophosphor (UCNP)‐based displays have received increased attention, with emerging reports on transparent displays utilizing multicolor upconversion luminescence from single UCNPs. For these display devices, color reproducibility is one of the most essential properties and the multicolor‐emitting UCNPs are required to exhibit a wide color gamut (WCG) for enhanced color reproducibility. However, achieving both high brightness and WCG properties simultaneously remains challenging for multicolor‐emitting single UCNPs. Here, bright red/green/blue (RGB) orthogonal luminescent core@sextuple‐shell (C@6S) UCNPs showing a WCG under 800, 980, and 1532 nm near‐infrared (NIR) light is reported. Luminescent properties of various C@6S UCNPs with 6 distinct R‐G‐B configurations are investigated and a green‐emitting core coated with a red‐emitting inner shell and a blue‐emitting outer shell satisfied high brightness and WCG properties. The green‐emitting core‐based C@6S UCNPs showed multicolor tunability with high brightness and the widest color gamut value of 94.2% of the National Television System Committee color space among RGB‐emitting core@multishell UCNPs. Furthermore, potential full‐color displays utilizing the transparent C@6S UCNP‐polydimethylsiloxane composite and NIR light sources are demonstrated. These findings provide the criteria for synthesizing the RGB‐emitting single UCNPs exhibiting high brightness and a WCG and would be beneficial for the realization of true 3D full‐color displays.
Nanoconfined and Chemically Bonded MnO@Mn2O3 Heterojunctions Within Carbon Nanotubes for Fibrous Supercapacitor with Ultra‐Long Cycle Stability
Authors: Zhang Juan , Gao Rui , Yang Xiaona , Ma Qianyi , Zhang Haoze , Zhao Weinan , Xu Qingli , Pan Aixi , Chen Xinyi , Wang Jian , Chen Ning , Wang Xinhou , Yu Aiping , Zhang Kun
Published: January 2025

Carbon‐based fibrous supercapacitors (FSSCs) are promising power sources for wearable electronics, often compounding with transition metal oxides (TMOs) to improve energy density. However, conventional methods introducing TMOs onto exterior surfaces of carbon‐based fibers typically degrade electrical transport and cycle stability. Herein, nanoconfined MnO@Mn2O3 heterojunctions within carbon nanotube (CNT) (MOIC) composite FSSCs stabilized by Mn─O─C bonds, exhibiting record cycle stability with 95.7% capacitance retention after 10 000 cycles and 89.4% after 50 000 cycles are reported. X‐ray absorption near edge structure (XANES), X‐ray diffraction, and X‐ray photoelectron spectroscopy (XPS) analyses confirm MnO@Mn2O3 heterostructure, which arises through a partial phase transformation from MnO to Mn2O3, as further supported by density functional theory calculations. Mn─O─C chemical bonds, as verified through XPS, extended X‐ray absorption fine structure, and XANES analyses, facilitate 3D electron transport, enabling MOIC composite fiber superior electrical conductivity than CNT fiber. The nanoconfinement of Mn2+ within CNTs, driven by capillary effects and electrostatic repulsion between protonated CNTs and Mn2+, preserves the clean exterior surfaces of CNTs. This configuration enables the successful wet‐spinning of MOIC composite fibers with three times the tensile strength of fibers without nanoconfinement. This work opens new pathways for designing carbon/metal oxide hybridized supercapacitors for wearable energy storage applications.
Nanoscale Metal‐Organic Framework Leveraging Water, Oxygen, and Hydron Peroxide to Generate Reactive Oxygen Species for Cancer Therapy
Authors: Zhu Zhong‐Hong , Zhang Le , Jia Shaorui , Ni Zhiqiang , Li Yun‐Lan , Zou Hua‐Hong , Yang Yutong , Hu Yating , Ding Dan , Tang Ben Zhong , Feng Guangxue
Published: January 2025

Spatiotemporally increasing intracellular reactive oxygen species (ROS) level represents a promising and effective antitumor approach, but is significantly hindered by insufficient ROS sources within the tumor. Herein, a Cu‐porphyrin based nanoscale metal‐organic framework (nMOF) CuIIMOF is reported, which inherently integrates chemodynamic therapy (CDT), photodynamic therapy (PDT), and photocatalytic capabilities to generate intracellular ROS storm for cancer immunotherapy. Unlike conventional porphyrin‐based MOFs, CuIIMOF features nearly orthogonally aligned porphyrin skeletons, minimizing π–π stacking and preventing ROS self‐quenching. The Fenton‐like reaction of CuIIMOF depletes glutathione (GSH) and catalyzes H2O2 to generate hydroxyl radical (·OH) for CDT. Intriguingly, its unique topology and energy levels enable CuIIMOF to photocatalyze the splitting of H2O into ·OH, overcoming the limitations of oxygen/H2O2 dependence in PDT and CDT. Moreover, the reduced CuICuIIMOF, formed during the Fenton‐like reaction, exhibits further enhanced lighted‐triggered ROS generation. Thus, the developed CuIIMOF and CuICuIIMOF nanosheets can utilize H2O2, O2, and H2O as the source to generate a remarkable intracellular ROS storm through a synergetic CDT/PDT/photocatalytic combination. Both in vitro and in vivo experiments further demonstrate that the spatiotemporally generated ROS could effectively provoke ferroptosis and immunogenic cell death, eliciting substantial anti‐tumor immune response for cancer immunotherapy.
Atomic Cluster Outperforms Single Atom in Hydrogen Evolution and Hydrazine Oxidation for Energy‐Efficient Water Splitting
Authors: Liu Chunhua , Wu Shuwen , Yang Yang , Wei Jinshan , Chen Shujing , Sun Xiao‐Qing , Luo Shuiping , Hussain Muhammad Bilal , Feng Renfei , Fu Xian‐Zhu , Liu Shao‐Qing , Luo Jing‐Li
Published: January 2025

The hydrazine‐assisted water splitting (HzAWS) is promising for energy‐saving hydrogen production. However, developing efficient bifunctional catalysts that exert hydrogen evolution reaction (HER) and hydrazine oxidation reaction (HzOR) at industrial‐grade current densities remains challenging. Here, RuC‐NiCoP catalyst, ruthenium clusters (RuC) immobilized onto NiCoP, is developed to elucidate the superior performance of RuC in enhancing bifunctional electrocatalytic activity over ruthenium single atoms (RuSA). The RuC‐NiCoP achieves current densities of 10 and 100 mA cm−2 for HER and HzOR with working potentials of −10 and −89 mV, respectively, outperforming RuSA‐NiCoP (−16 and −65 mV). During HzAWS, a cell voltage reduction of 1.77 V at 300 mA cm−2 is observed compared to overall water splitting. Density functional theory calculations reveal that RuC improves the adsorption energy for H2O and N2H4, optimizes the H* intermediate desorption, and reduces the dehydrogenation barrier from *N2H3 to *N2H2. Additionally, the direct hydrazine fuel cell with a RuC‐NiCoP anode delivers an impressive power density of 226 mW cm−2 and enables a self‐powered hydrogen production system, achieving an unprecedented hydrogen production rate of 4.9 mmol cm−2 h−1. This work offers a new perspective on developing efficient sub‐nanoscale bifunctional electrocatalysts and advancing practical energy‐saving hydrogen production techniques.
1.6‐Inch Transparent Micro‐Display with Pixel Circuit Integrated microLED Chip Array by Misalignment‐Free Transfer
Authors: Hwang Kyungwook , Hwang Junsik , Kim Yongchan , Song Sanghoon , Kong Kiho , Oh Youngtek , Chung Deukseok , Yu Min‐Chul , Kim Dongho , Park Joon‐Yong , Moon Jinho , Kim Sungi , Kim Tae‐Gon , Lee Gyuhyung , Yeom Min Jae , Kim Joosung , Shin Dong‐Chul , Kim Dong Kyun , Hong Seog Woo , Kim‐Lee Hyun‐Joon , Jeong Jaewook , Lee Hojin , Yoo Geonwook
Published: January 2025

Recent advances in mass transfer technology are expected to bring next‐generation micro light‐emitting diodes (µLED) displays into reality, although reliable integration of the active‐matrix backplane with the transferred µLEDs remains as a challenge. Here, the µLED display technology is innovated by demonstrating pixel circuit‐integrated micro‐LEDs (PIMLEDs) and integrating them onto a transparent glass substrate. The PIMLED comprises of low‐temperature poly‐silicon transistors and GaN µLED. The square‐shaped PIMLED is designed to secure a larger process margin but to reduce misalignment in the subsequent bonding process. Its unique four‐fold rotational symmetric design together with concentric circular pixel electrodes of the substrate makes their massive transfer compatible with intrinsic randomness of fluidic‐based transfer and free from angular misalignment during wafer bonding. The vertically integrated pixels show similar optical and electrical properties regardless of four possible arrangements. It is demonstrated that a 96 × 96 PIMLED display on a transparent glass substrate, which is expected to open a door to novel form‐factor free and transparent µLED displays.
Adaptive sampling Bayesian algorithm for constrained black‐box optimization problems
Authors: Fan Shuyuan , Hong Xiaodong , Liao Zuwei , Ren Congjing , Yang Yao , Wang Jingdai , Yang Yongrong
Published: January 2025

Constrained black‐box optimization (CBBO) has become increasingly popular in process optimization. Algorithms often encounter difficulties in balancing feasibility and optimality, with some even failing to find feasible solutions. This article introduces an adaptive sampling Bayesian optimization algorithm (ASBO) to solve CBBO problems effectively. The developed infill sampling criterion introduces an adaptive acquisition function to facilitate multistage optimization. The three stages consist of exploring feasible solutions, balancing feasibility and optimality, and optimizing. Furthermore, a hybrid method is proposed for complex problems. A gradient‐based optimizer (GBO) aids in constructing the posterior distribution, thereby enhancing the identification of feasible regions. Additionally, four auxiliary strategies are developed to enhance stability and accelerate convergence in simulation‐based optimization. The effectiveness of the proposed algorithm is validated through three benchmark problems and two process optimization cases. Comparative analysis against state‐of‐the‐art algorithms demonstrates better iteration efficiency of ASBO algorithms.
Droplet contact numbers and contact probabilities in liquid‐liquid dense‐packed zones
Authors: Sibirtsev Stepan , Thiel Lukas , Kirsanov Andrey , Jupke Andreas
Published: January 2025

Dense‐packed zones (DPZs) are crucial in designing equipment for liquid‐liquid phase separation processes, as the DPZ height affects apparatus size. This article presents an open‐access simulation approach to determine droplet contact numbers and probabilities, which are vital for modeling the deformation and coalescence of polydisperse droplets in a DPZ. The simulation is applied to three technical cases to assess how droplet size distribution (DSD) shapes impact contact numbers and probabilities. Sensitivity analysis reveals that broader DSDs and larger droplet classes lead to higher contact numbers. In contrast, contact probability is primarily determined by droplet class diameter and its number probability within the DSD, showing an almost linear relationship. These results highlight the significance of DSD shape and droplet class diameter in predicting droplet contact numbers and probabilities in DPZs, providing valuable insights for future modeling of liquid‐liquid phase separation.
A mechanism linking sleep with CSF‐to‐Blood toxins clearance
Authors: Alperin Noam , Burman Ritambhar
Published: January 2025

Background

Clearance of brain toxins occurs during sleep, although the mechanism remains unknown. Previous studies implied that the intracranial aqueductal cerebrospinal fluid (CSF) oscillations are involved, but no mechanism was suggested. The rationale for focusing on the aqueductal CSF oscillations is unclear. This study focuses on the cranio–spinal CSF oscillation and the factors that modulate this flow. We propose a mechanism where increased cranio–spinal CSF movements enhance CSF‐to‐blood metabolic waste clearance through the spinal CSF re‐absorption sites, by increased the transfer of toxins from the toxin‐ rich cranial CSF to the toxin‐poor spinal CSF. A recent study demonstrating that disturbed sleep impairs CSF‐to‐blood but not brain to‐CSF clearance, supports the fundamentals of our proposed mechanism.

Method

Eight healthy subjects underwent phase‐contrast magnetic resonance imaging to quantify the effect of respiration on the cranio–spinal CSF oscillations. Maximal CSF volume displaced from the cranium to the spinal canal during each respiration and cardiac cycle were derived as measures of cranio–spinal CSF mixing level, Displaced CSF volume was measured during normal breathing (NB) and Slow deep abdominal breathing (SAB). Displaced CSF volume between the 3rd and 4th ventricl3es during normal breathing were also measured.

Result

Transition from normal to slow and abdominal breathing resulted in a 56% increase in the maximal displaced CSF volume. Maximal change in the arterial–venous blood volume, which is the driving force of the CSF oscillations, was increased by 41% during slow abdominal breathings. Displaced CSF volume between the ventricles during each oscillation were about 10‐fold smaller than the discalced CSF volume between the ventricles.

Conclusion

Cranio–spinal CSF oscillations are driven by the momentary difference between arterial inflow and venous outflow. Breathing modulates the CSF oscillation through changes in the venous outflow. The amount of toxins being transferred to the spinal canal during each respiratory cycle is significantly increased during slow and deeper abdominal breathing, which explains enhanced CSF‐to‐blood toxins clearance during slow‐wave sleep and poor clearance during disrupted sleep.
Prefrontal Hemodynamic Activity during Working Memory Challenges: Investigating Stimulus Influence
Authors: Lim Seungju , Park Ji‐Hyuk
Published: January 2025

Background

Research on hemodynamic responses in the prefrontal cortex during working memory tasks has mainly been performed in cognitive neuroscience research. However, the specific stimuli contributing to working memory deficits in major depressive disorder (MDD) are currently lacking. This study aims to compare working memory performance and prefrontal cortex activation in individuals with MDD and healthy controls during working memory tasks involving textual, visual, and emotional stimuli.

Method

Functional near‐infrared spectroscopy was utilized to record hemodynamic responses from 71 adults (30 with MDD and 41 controls) during the 2‐back tasks with four stimulus types: numbers, letters, polygons, and facial expressions. Working memory performance was measured by accuracy and reaction time during the tasks, and hemodynamic responses were collected by oxyhemoglobin (HbO) activation of the prefrontal cortex during the tasks.

Result

MDD demonstrated lower working memory performance than controls during polygon and facial expression‐based 2‐back tasks, while there was no significant difference under number and letter conditions. MDD under the polygon stimulus exhibited abnormal HbO activation in the bilateral ventrolateral prefrontal cortex compared to controls, while under the facial expression stimulus, it showed exclusive abnormal HbO activation in the left medial prefrontal cortex, bilateral orbito prefrontal cortex, and bilateral ventrolateral prefrontal cortex.

Conclusion

These findings indicate the importance of stimuli that require cognitive processing not only for logical aspects, such as polygons, but also for emotional aspects, like facial expressions, in evaluating hemodynamic responses of prefrontal cortex and working memory abilities in individuals with MDD.
Subtype‐specific patterns of tau pathology in Alzheimer’s and related disorders
Authors: Hobbs Diana A , Doering Stephanie , McCullough Austin A. , Millar Peter R , Flores Shaney , Keefe Sarah J. , Sotiras Aristeidis , Benzinger Tammie L.S. , Day Gregory S , Gordon Brian A.
Published: January 2025

Background

Alzheimer disease (AD) involves neurodegenerative disorders with progressive cognitive decline. Atypical presentations like Posterior Cortical Atrophy (PCA) and Logopenic Variant Primary Progressive Aphasia (lvPPA) exhibit distinct clinical profiles. PCA affects the posterior parietal and occipital lobes, causing visuospatial deficits, while lvPPA manifests as language impairment in the temporoparietal region. Understanding the biological underpinnings of these variants is crucial for deciphering AD’s heterogeneity.

Method

Participants diagnosed with AD dementia (n = 54, female = 25, Age: 75.23±6.52), PCA (n = 9, female = 8, Age: 62.78±7.21), and lvPPA (n = 6, female = 2, Age: 66.33±6.38) from the Knight Alzheimer Disease Research Center (Knight ADRC) underwent 18F‐AV‐1451 tau‐PET imaging. Tau deposition, along with nine biological properties, was mapped to the cortical surface (Figure 1A): gene expression, myelin, cortical thickness, sensorimotor association axis, evolutionary expansion, cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral metabolic rate of glucose (CMRglu) (Figure 1B). Correlation matrices and generalized linear models (GLMs) assessed relationships between tau accumulation and biological properties.

Result

A correlation matrix (Figure 2A) shows significant positive associations (p<0.05) between evolutionary expansion patterns and tau accumulation in AD (r = 0.53), PCA (r = 0.29), and lvPPA (r = 0.56); and gene expression in PCA (r = 0.51). Conversely, strongest negative associations were observed in AD (r = ‐0.38, r = ‐0.15) and lvPPA (r = ‐0.18, r = ‐0.28) for CBF and myelin mapping, respectively, and in PCA (r = ‐0.25, ‐0.23) for cortical thickness and sensorimotor association axis. GLMs demonstrated significant relationships between cerebrovascular health and evolutionary expansion with tau measures across all groups. AD (r = ‐0.52) and PCA (r = ‐0.19) exhibited negative associations with gene expression and myelin mapping, respectively. Additionally, lvPPA (r = 0.39) displayed positive association with the sensorimotor association cortex.

Conclusion

Results elucidate distinct tau deposition patterns in AD, PCA, and lvPPA, providing insights into subtype‐specific pathophysiology. The correlation matrix and GLMs highlight the significance of evolutionary expansion and cerebrovascular health in tau accumulation. Associations underscore the complex interplay of gene expression, myelin mapping, and cortical thickness with tau pathology. Findings contribute to understanding heterogeneity within AD spectrum disorders, emphasizing the multifaceted nature of neurodegenerative processes. Further research promises refined diagnostic and therapeutic strategies tailored to distinct neurobiological profiles in AD, PCA, and lvPPA.
Mixed pathologies and cognitive outcomes in older persons ‘possibly’ eligible for anti‐amyloid treatment: a community‐based study
Authors: Kapasi Alifiya , James Bryan D , Yu Lei , Bennett David A. , Boyle Patricia A , Schneider Julie A.
Published: January 2025

Background

The recent approval of two anti‐amyloid antibodies, Aducanamab and Lecanamab, have set the stage for the next generation of anti‐amyloid treatments. Despite the capability of these treatments to lower Aβ brain levels, there is thus far limited clinical efficacy on cognitive outcomes. Because eligibility for treatment includes individuals with MCI or mild dementia, that often harbor mixed pathologies, the cognitive impact of other brain pathologies may be important. This study investigated mixed brain pathologies from autopsied persons that would be considered eligible for anti‐amyloid treatment and the association of pathologies with rate of decline in global cognition and five cognitive domains.

Method

Eligibility was defined based on having an MMSE score ≥ 20, a clinical diagnosis of MCI or Alzheimer’s dementia, and a level of Aβ pathology that would be indicative of having a positive amyloid PET scan (CERAD score≥moderate). We examined the number and types of co‐pathologies. Mixed‐effect models were employed to examine association of pathologies (β‐amyloid, tangles, LATE‐NC, infarcts, and LB) with rate of decline in global cognition and across 5 cognitive domains.

Result

Among 428 older autopsied persons (mean age at death = 90 years) considered possibly eligible for anti‐amyloid treatment, 58% had MCI and 42% had mild dementia. The majority (94%) had a pathologic diagnosis for AD, of which most had ≥ 1 co‐pathology; 43% had +1 co‐pathology, 22% had +2 co‐pathologies, and 3% had +3 co‐pathologies. Regarding type of co‐pathologies, 37% had AD + infarcts, 36% had AD + LATE, and 24% had AD + LB. In mixed‐effect models, tangles were associated with a faster rate of global cognitive decline, specifically in the domains of episodic (estimate = ‐0.04; SE = 0.01; p<0.001) and semantic memory (estimate = ‐0.02; SE = 0.01; p = 0.001). Independent of tangles, LATE‐NC and β‐amyloid were also associated with decline in episodic (estimate = ‐0.03, SE = 0.01; p = 0.004) and semantic memory (estimate = ‐0.02; SE = 0.01, p = 0.04), respectively. Infarcts and LB were not associated with decline in global cognition or any cognitive domains.

Conclusion

Mixed pathologies are common in this group of community‐dwelling older persons possibly eligible for anti‐amyloid treatments. Tangles and LATE‐NC pathologies drive late‐life cognitive decline, especially episodic memory.
A comparison of cognitive factors identified by Exploratory Factor Analysis of the original ADAS‐cognitive subscale and a novel extended version in mild cognitive impairment and Alzheimer’s dementia
Authors: Overby Mark S. , McGinity Sean , Botchway Albert , Zec Ronald F. , Ala Thomas A. , Settelmyer Zachary , Ranjit Eukesh , Shah Raj C. , Hascup Erin R. , Trivedi Mehul A.
Published: January 2025

Background

The original Alzheimer’s Disease Assessment Scale – Cognitive Subscale (oADAS) is one of the most common measures of cognition used in clinical trials of Alzheimer’s dementia (AD). Despite this, the oADAS has faced criticism for lacking sensitivity to Mild Cognitive Impairment (MCI), potentially due to ceiling effects for certain subsets. Many attempts have been made to improve the sensitivity of the oADAS to MCI by including additional subtests. We previously used exploratory factor analysis (EFA) on the subtests from the oADAS and a novel extended version of the ADAS (eADAS). We identified two factors for both the oADAS (general and praxis factors) and the eADAS (memory/speed and general factors). In the present study, we examined group differences between normal controls, MCI, and AD on the four factors previously identified.

Method

This analysis included data from 680 normal controls above the age of 60 who were participants in the SIU Longitudinal Cognitive Aging Study (SIU LCAS), 63 individuals with amnestic MCI (MCI), and 51 individuals with possible/probable AD. Participants were administered the oADAS using standardized procedures along with an extended version (eADAS) that included additional measures of processing speed, language, learning/memory, and visuospatial skills. A 3‐group ANCOVA was completed between control, MCI, and AD groups and the four factor components. Age, gender, and education were included as covariates.

Result

For the oADAS, a general factor was able to discriminate between the three groups (p’s<0.001) while a praxis factor showed differences between control and AD groups and between MCI and AD groups (p’s<0.001) but not between MCI and controls (p>.90). For the eADAS, both a memory/speed factor and a general factor were able to significantly discriminate between all three groups (p’s<0.05).

Conclusion

This study demonstrated that most of the identified cognitive factors were able to discriminate between the three groups with the exception of the praxis factor from the oADAS, which did not demonstrate significant differences between the MCI and control groups. More research is needed to further determine which subtests from the oADAS and eADAS are most sensitive to cognitive changes in normal and abnormal cognitive aging.
Harnessing the Potential of Human iPSC‐derived Microglia‐like Cells as Antigen Presenting Cells for MAIT Cells to Study AD Pathology
Authors: Afify Reham , Brutkiewicz Randy R
Published: January 2025

Background

Microglia are dominant immune cells residing in the brain that regulate brain homeostasis and T‐cell responses. An important immune function of microglia involves presenting microbial antigens to mucosal‐associated invariant T (MAIT) cells; MAIT cells recognize microbial vitamin B‐derived metabolites presented by the MHC class I‐like molecule, MR1. Our recent findings highlighted a detrimental role for the MR1/MAIT cell axis in Alzheimer’s disease (AD) using the 5XFAD mouse model. Here, our work is focused on how the MR1/MAIT cell innate immune axis in humans contributes to AD, using iPSC‐derived human microglia‐like cells (iMG) to provide potential mechanistic insights underlying the MR1/MAIT cell axis in AD. As an initial evaluation, we have assessed the activation of iMG and their potential as functional antigen presenting cells (APC) to MAIT cells when exposed to a microbe that can provide a MR1‐presented, MAIT cell‐specific antigen, such as from E. coli.

Methods

Initially, we will generate iMG from healthy donors that will be incubated with E. coli for the assessment TNF‐α levels using ELISA as a readout of microglial activation. Subsequently, coculture experiments with human MAIT cells and E. coli‐stimulated iMG will provide an initial evaluation of microglial MR1‐dependent MAIT cell activation via MR1‐dependent antigen presentation, monitored by MAIT cell production of various cytokines measured by ELISA.

Results

We expect that iMG will produce increased levels of TNF‐α in response to E. coli compared to the control group. Similarly, we anticipate elevated cytokine levels secreted by MAIT cells via an MR1‐dependent pathway.

Conclusions

These experiments will allow us to apply our human iPSC‐based model to studying human microglia as APC and pave the way for a broader understanding of the contributions of the MR1/MAIT cell axis in AD. To our knowledge, our proposed study will be the first of its kind to utilize iMG as APC for human MAIT cells.
Impact of age at immigration on neuropsychological assessments among older South Asian Americans
Authors: Kota Karthik , Hundal Jasdeep , Sotelo Victor , Dawson Allison , Sarkar Shromona , Hu William T.
Published: January 2025

Background

South Asian (SA) Americans are underrepresented in US Alzheimer’s disease and related dementias (ADRD) research. Despite sharing common languages, SA Americans differ from those in South Asia in education, health‐related behaviors, and environmental exposures. NYC/NJ‐area SA communities overwhelmingly revealed English‐based neuropsychological testing preference given that many speak non‐Hindi languages. Further complicating testing is evidence of non‐cognitive/linguistic factors influencing SA adults’ performance. For example, mean performance on the language‐independent Trail Making Test A (TMT‐A) among older adults across five Indian cities was <1st percentile. We thus recruited an older SA American cohort without subjective cognitive complaints to undergo neuropsychological testing, correlating performance with immigration‐related variables.

Method

65 SA participants completed neuropsychological testing, assessing memory (logical memory, CERAD word list, Benson complex figure), attention/speed (forward digit span [FD], TMT‐A), executive (reversed digit span [RD], TMT‐B, symbol digit substitution test [SDST], letter‐guided fluency [FAS]), language (Multilingual Naming Test [MINT], Boston Naming Test [BNT‐60], and visuospatial functions (Judgement of Line Orientation [JOLO]). Z‐scores derived from the National Alzheimer’s Coordinating Center calculators underwent linear regression modeling to determine influence from age (first learning English, at immigration), years in the US, and education (native country vs US).

Result

Participants (30 women and 35 men) had a median age of 65 years (range 24‐86) and median education of 18 years (range 12‐20), with a median 16 in home country (range 3‐20); they were a median age of 30 (range 8‐69) years at immigration and had a median US residency of 32 years (range 4‐59). Age at immigration (story recall, TMT‐A, MINT, BNT, category fluency‐animals, JOLO) and years in the US (category fluency‐vegetables, word list learning and recall) had the greatest influence on neuropsychological performance, and two tests (story learning, letter‐guided fluency) were influenced by both. Five tests (Benson complex figure immediate and delayed recall, FD, RD, TMT B) were uninfluenced by immigration‐related factors.

Conclusion

In addition to age, gender, and education, neuropsychological performance interpretation among SA Americans must account for age at immigration, years in the US, or both. Acculturation and familiarity with aptitude testing – potentially in language‐independent ways – likely influenced SA Americans’ neuropsychological analysis outcomes.
The Role of Prospective Memory in Predicting Neuropsychological Functioning in Mild Cognitive Impairment and Alzheimer’s Disease
Authors: Kozuki Jordan , Collins Andrea , Reyes Fabiola Amaya , Herrera Summer , Cruz‐Lopez Keely , Woo Ellen
Published: January 2025

Background

Prospective memory (PM), the ability to execute an intended action in the future (e.g., taking medications), is impaired in Alzheimer’s disease (AD). This study examines the utility of subjective and objective measures of PM in predicting neuropsychological functioning across five cognitive domains in healthy aging, mild cognitive impairment (MCI), and AD.

Method

Participants included 58 healthy older controls, 65 persons with MCI, and 18 individuals with AD. Subjective reports of PM included both participant and informant ratings on the Prospective‐Retrospective Memory Questionnaire (PRMQ). Additionally, an objective PM task was completed throughout a neuropsychological test battery. Simple objective PM was measured by asking participants to remember to execute the single action of requesting a pill after each neuropsychological test performed. Complex objective PM was measured by asking participants to request a specific number of pills depending on whether a memory or non‐memory test was completed. Composite neuropsychological test scores were used to assess the domains of language, memory, executive functioning, visuospatial skills, and attention.

Result

Regression analyses revealed that in MCI, informant reports of PM predicted executive functioning. In healthy aging and MCI, both types of objective PM predicted memory performance. PM did not predict language, visuospatial skills, or attention in any group.

Conclusion

Among healthy older adults and those with MCI, objective measurements of prospective memory predict episodic memory outcomes. When participants begin to exhibit cognitive decline, as seen in MCI, informant reports are additionally beneficial and predict executive functioning. This research supports previous findings that prospective memory is multifactorial and involves both memory and executive functioning. Overall, this research also suggests that the assessment of prospective memory has utility for understanding the early decline of cognitive domains traditionally evaluated in MCI.
Using proximity labelling to investigate astrocytic protein profile changes in response to amyloid pathology in a mammalian model of Alzheimer’s disease
Authors: Desai Perlina , Carcamo Lorena Arancibia , De Strooper Bart
Published: January 2025

Background

Astrocytes are a numerous and diverse glial subtype specialised to carry out distinct roles involving maintaining homeostasis and effective functioning of the nervous system. To do so effectively, they respond to and secrete various proteins. In addition, astrocytes have been linked to Alzheimer’s disease (AD), where they are believed to become reactive and contribute to neuroinflammation. A key feature of this reactive gliosis is the secretion of inflammatory mediators. Although in some instances this can be protective, in others, secretion of inflammatory mediators can be harmful, thus possibly contributing to AD pathology. At present, there remains a limited understanding of global astrocytic membrane and extracellular protein profiles and potential AD‐associated changes.

Method

Here, we aimed to address this using a proximity labelling‐based approach. Specifically, we used a viral construct containing TurboID targetted to the ER under a GFAP promoter in order to study astrocyte‐specific proteins trafficked through the classical secretory pathway in an AD mouse model.

Result

After characterising the construct, we investigated changes in proteins between AD and controls over time in response to amyloid pathology. We have identified protein changes which are now being validated using mammalian biofluids such as CSF and plasma.

Conclusion

This work enables a better understanding of astrocyte‐specific membrane and extracellular protein changes as the disease progresses in a mammalian model of AD. An enhanced understanding of this will not only provide insight into astrocyte biology more generally, but may ultimately be vital for identification of novel biomarkers and therapeutic targets for detecting and treating AD.
Clusters of modifiable risk factors provide resilience to the cognitive effects of β‐amyloid pathology in aging
Authors: Bhade Mohini , Pezzoli Stefania , Giorgio Joseph , Ward Tyler J. , Landau Susan M. , Jagust William J.
Published: January 2025

Background

Although it has been estimated that modifiable risk factors account for around 40% of population variability in dementia risk, understanding how risk factors are related to one another and to brain pathology and cognition has been challenging. We used a clustering approach to examine patterns of risk factor interrelationships and to investigate how these patterns affect relationships between pathology and cognition.

Method

We collected risk factor data concerning health, lifestyle, sleep, and personality from 149 cognitively normal older adults (73±6.2 years), as well as PET‐measured amyloid (11C‐Pittsburgh compound‐B, PiB) and, in a subsample (n = 126), PET‐measured tau (18F‐Flortaucipir, FTP). All participants completed longitudinal neuropsychological testing (follow‐up 8.1±4.2 years). K‐means clustering was used to assign participants to different risk profiles that reflected how risk factors were interrelated. Linear mixed‐effects models were used to assess associations between decline in 1) episodic memory (EM) and 2) non‐memory (NM) cognition composite scores, with cluster assignment and PiB‐status (±) or entorhinal FTP uptake as predictors. Analyses were age and sex adjusted.

Result

K‐means clustering generated 3 distinct risk‐related profiles, with more favorable profiles seen for participants in cluster 1 (physical/cognitive activity, education) and cluster 2 (sleep, depression, personality) than cluster 3 (Figure 1). In a model predicting NM decline with PiB‐status as a predictor, we observed a significant three‐way interaction between PiB‐status, cluster, and time (p<0.01) with an attenuated effect of Aβ on NM decline in cluster 1 (β = 3.7, p<0.01) and cluster 2 (β = 3.7, p<0.01) compared to cluster 3. A model predicting EM revealed no significant interaction between cluster, PiB‐status and time (Figure 2). While a significant entorhinal tau x time effect was observed in a model predicting EM decline, cluster assignment did not modify this relationship. Results were similar when APOE4 status was included in the models.

Conclusion

Favorable risk profiles (cluster 1 and 2) attenuated the effect of Aβ, but not tau, on cognitive decline. These findings suggest that different risk profiles moderate pathology‐cognition relationships, and demonstrate that different factors may operate together in reducing risk. This highlights the role of groups of modifiable resilience factors in mitigating the effects of Aβ deposition.
Relationships Between NIH Toolbox Cognitive Battery Subtests and In Vivo Amyloid and Tau in People with Amnestic Mild Cognitive Impairment and Dementia of the Alzheimer’s Type
Authors: Fox‐Fuller Joshua T , Petscavage Kenneth , Rogers Ginny , Koeppe Robert A. , Albin Roger L. , Iordan Alexandru D , Hampstead Benjamin M. , Rahman‐Filipiak Annalise
Published: January 2025

Background

The computerized NIH Toolbox Cognition Battery (NIHTB‐CB) was designed to assess cognitive functioning across the lifespan. Previous studies demonstrated that NIHTB‐CB measures discriminate between healthy controls (HCs), individuals with amnestic mild cognitive impairment (aMCI), and individuals with dementia of the Alzheimer’s type (DAT). Scores on NIHTB‐CB tasks also correspond with performance on well‐validated neuropsychological measures of the same cognitive domains. We are among the first to evaluate how NIHTB‐CB subtest performances and in vivo Alzheimer’s disease (AD) pathology are related in people with aMCI and DAT.

Method

As part of a larger clinical trial in the Research Program on Cognition and Neuromodulation Based Interventions, 139 participants with aMCI or DAT (Table 1) underwent neuropsychological assessment, including five iPad NIHTB‐CB subtests: Flanker, List Sort, Card Sort, Pattern Separation, and Picture Sequence. Participants also completed positron emission tomography (PET) scans of amyloid and tau. Amyloid PET scans were normalized to the centiloid value, and tau PET standardized uptake value ratios (SUVr) were merged into a bilateral meta‐region‐of‐interest based on Braak staging. Stepwise linear regressions were used to evaluate the relationship between age and education with NIHTB‐CB subtests (Model 1), as well as in vivo AD pathophysiology with NIHTB‐CB subtests beyond age and education (Model 2).

Result

In vivo amyloid was significantly related to List Sort (β = ‐0.31, p<.001, ΔR2 = .09) and Card Sort performance (β = ‐0.25, p = .004, ΔR2 = .06), explaining significantly more subtest variance beyond age and education. In vivo tau was significantly related to performance on all NIHTB‐CB subtests and explained significantly more subtest variance than demographic factors (Flanker: β = ‐0.25, p = .004, ΔR2 = .06; List Sort: β = ‐0.40, p<.001, ΔR2 = .15; Card Sort: β = ‐0.32, p<.001, ΔR2 = .10; Pattern Separation: β = ‐0.18, p = .04, ΔR2 = .03; Picture Sequence: β = ‐0.23, p = .01, ΔR2 = .05).

Conclusion

In vivo AD pathophysiology is related to NIHTB‐CB subtest performances in individuals with aMCI or DAT and explains significantly more NIHTB‐CB subtest variance than demographic factors alone. This work adds growing support to the relationship between NIHTB‐CB subtests and in vivo AD biomarkers.
Sex hormones and white matter hyperintensities in midlife women in the MsBrain study
Authors: Thurston Rebecca C , Wu Minjie , Chang YueFang , Aizenstein Howard J , Derby Carol A. , Maki Pauline M
Published: January 2025

Background

Sex hormones are frequently implicated in the development of cerebral small vessel disease among midlife women. However, few studies directly measure endogenous sex hormones and consider them in relation to white matter hyperintensities (WMH), indicators of cerebral small vessel disease. Further, existing work on hormones, menopause, and the brain typically focuses on ovarian estradiol (E2), with limited consideration of estrone (E1), the primary postmenopausal estrogen, or follicle stimulating hormone (FSH), an indicator of ovarian age. We tested the associations of E2, E1, and FSH in relation to WMH volume (WMHV) among late midlife women. We considered both whole brain WMHV and the spatial distribution of WMHV.

Methods

222 women ages 45‐67 (mean = 59.29 years, 99% postmenopausal), not taking hormone therapy, and free of a history of cardiovascular disease were recruited for the MsBrain study. Procedures included physical measures; phlebotomy for sex hormones (E1, E2, FSH; estrogens assessed via LC‐MS/MS), glucose, insulin, and lipids; and 3T magnetic resonance imaging. Associations of E1, E2, and FSH with WMHV were tested in linear regression models with covariates age, race/ethnicity, education, and in a separate step, adjusted for cardiovascular disease (CVD) risk factors [body mass index, smoking, blood pressure level and medications, insulin resistance, lipids]. Additional models considered regional WMHV (deep, periventricular, frontal, temporal, parietal, occipital).

Results

In age, race, and education‐adjusted models, lower E2 [B(SE) = ‐.12(0.05), p = .02], lower E1 [B(SE) = ‐0.26(0.10), p = 0.007], and higher FSH [B(SE) = 0.26(0.07, p = 0.0005] were each associated with greater whole brain WMHV. When further controlling for CVD risk factors, associations of E1 [B(SE) = ‐.21(.10), p = .04] and FSH [B(SE) = .18(.09), p = .04] (but not E2) to whole brain WMHV remained (Figure 1). Considering the spatial distribution of WMHV, lower E1 was associated with more frontal, deep, and temporal WMHV; and higher FSH with more frontal and periventricular WMHV.

Conclusions

Findings indicate the importance of endogenous sex hormones to late midlife women’s cerebrovascular health. They underscore the value, when investigating aging women’s brain health, of moving beyond a sole focus on E2 to also consider E1 and FSH, hormones particularly relevant in the postmenopause.
Phenotype Spectrum of TRPM3‐Associated Disorders
Authors: Jolitz Laura , Helbig Ingo , Fitzgerald Mark P. , McKeown Ruggiero Sarah , Cohen Stacey , Angelini Chloe , Vallespin Elena , Michaud Vincent , Gerasimenko Anna , Cogne Benjamin , Isidor Bertrand , Keren Boris , Dyment David , Heron Delphine , Karstensen Helena Gásdal , Cuppen Inge , Christodoulou John , Wilson Meredith , Lake Nicole J. , Biskup Saskia , Syrbe Steffen , Mori Takayasu , Becker Lena‐Luise , Kaindl Angela M.
Published: January 2025

Objective

Monoallelic variants in the transient receptor potential melastatin‐related type 3 gene (TRPM3) have been associated with neurodevelopmental manifestations, but knowledge on the clinical manifestations and treatment options is limited. We characterized the clinical spectrum, highlighting particularly the epilepsy phenotype, and the effect of treatments.

Methods

We analyzed retrospectively the phenotypes and genotypes of 43 individuals with TRPM3 variants, acquired from GeneMatcher and collaborations (n = 21), and through a systematic literature search (n = 22). We included all patients with a pathogenic TRPM3 variant.

Results

The median age at the time of the study was 10 years, with a preponderance of girls (60%) versus boys (40%). Frequent findings were developmental delay and/or intellectual disability (93%), global or axial hypotonia (77%), ocular involvement (70%), musculoskeletal anomalies (65%), and dysmorphic features (58%). Epilepsy was diagnosed in 31 patients (72%), classified in all as developmental and epileptic encephalopathy with or without spike wave activation in sleep (DEE/DEE‐SWAS). Patients with the variant p.Val1002Met (n = 24) significantly more often had developmental delay and epilepsy. The most effective anti‐seizure medication was primidone. All treated patients showed an improvement in seizure frequency, motor and speech development, and/or learning capability with this drug.

Interpretation

Developmental delay/intellectual disability and epilepsy are dominant phenotypic features in patients with TRPM3 variants. Given that epilepsy can negatively impact development, screening for awake and sleep electroencephalogram abnormalities and other manifestations are essential to offer early intervention. The TRPM3 channel blocker primidone has shown promising effects and should be considered in every child with a TRPM3 gain‐of‐function variant. ANN NEUROL 2025;97:561–570
Entwicklung Konformationsbeschränkter Makrozyklen als Verbesserte FKBP51‐Inhibitoren durch Systematische Linker‐Derivatisierung
Authors: Spiske Moritz , Meyners Christian , Bauder Michael , Repity Maximilian , Brudy Christian , Sugiarto Wisely Oki , Achaq Hanaa , Geiger Thomas M. , Hausch Felix
Published: January 2025

Makrozyklen werden zunehmend als vielversprechende Strukturklasse zur Bindung für mit herkömmlichen Arzneistoffen schwer erreichbare intrazelluläre Proteine angesehen. Jedoch sind Strategien, bioaktive azyklische Moleküle zu Makrozyklen mit verbesserten Eigenschaften zu entwickeln in der aktuellen Forschung unterrepräsentiert. In der vorliegenden Studie wurde die Derivatisierung des Linkers als Ansatz zur Optimierung des pharmakologischen Profils von Makrozyklen untersucht. Unter Verwendung des FK506‐bindenden Proteins 51 (FKBP51) als Modellsystem wurden über 140 Makrozyklen mit systematisch derivatisierten Linkern hergestellt. Zwei Grundgerüste wurden als vielversprechende für die anschließende Optimierung identifiziert. Überraschenderweise zeigte die Analyse von Co‐Kristallstrukturen, dass diese identifizierten Grundgerüste eine Vielfalt von dreidimensionalen (3D) Konformationen einnehmen können, die die Basis für unterschiedliche 3D‐Gerüste darstellen. Dies führte zu einer Reihe von Makrozyklen mit durchweg verbesserter Affinität, Plasmastabilität und Wasserlöslichkeit im Vergleich zu den linearen Vorläufern oder den Makrozyklen mit unfunktionalisierten Linker‐Strukturen. Diese Ergebnisse machen deutlich, dass die Linkeroptimierung und ‐derivatisierung großes Potential für die Entwicklung makrozyklischer Arzneistoffe darstellt. Außerdem unterstreicht die Studie die Notwendigkeit, die Entwicklung makrozyklischer Gerüste auch auf dreidimensionaler Ebene zu betrachten.
Construction of Linear Tetramer‐Type Acceptors for High‐Efficiency and High‐Stability Organic Solar Cells
Authors: Zeng Rui , Deng Jiawei , Xue Xiaonan , Tan Sengke , Kan Lixuan , Lin Yi , Zhong Wenkai , Zhu Lei , Han Fei , Zhou Yuhao , Gao Xingyu , Zhang Ming , Zhang Yongming , Xu Shengjie , Liu Feng
Published: January 2025

Thanks to the development of non‐fullerene acceptor (NFA) materials, the photovoltaic conversion efficiency (PCE) of organic solar cells (OSCs) has exceeded 20 %, which has met the requirements for commercialisation. In the current stage, the main focus is to balance the performance and stability. It has been shown that all‐polymer formulation can improve device stability, however, PCE is not in satifsfaction, and the batch‐to‐batch variation leads to quality control issues. In this work, we constructed monodispersed tetramer NFA materials named G‐1 and G‐2, to best integrate the merits of small molecule and polymer. Density functional theory (DFT) calculations and experimental results showed that different connecting units at the centre could significantly affect the molecular planarity and thin film morphology. The alkene‐bonded tetramer G‐1 had a more regioregular structure, which leads to better molecular planarity, and more ordered packing in thin film. More importantly, the oligomeration induced a favourable face‐on orientation, achieved a lower binding energy and exhibited a higher photoluminescence yield. As a result, the exciton and charge carrier kinetics was optimized with reduced non‐radiative energy loss. The OSC based on PM6 : G‐1 achieved a PCE of 19.6 %, which is the highest PCE reported so far for oligomer‐based binary OSC. In addition, the device stability was largely improved, showing a lifetime over 10000 hours in the inverted OSC device.