bluuebunny/crossref_metadata_2025 huggingface dataset:
Sulfonate Additive Simultaneously Suppresses Interstitials and Vacancies Toward Efficient and Stable Perovskite Quantum Dot LEDs
Authors: Fang Tao , Yuan Shichen , Li Xiansheng , Shan Qingsong , Zhou Yihui , Xu Bo , Liu Gaoyu , Zhang Shengli , Li Xiaoming , Li Weijin , Fan Zhiyong , Zeng Haibo
Published: December 2023

Defect suppression via precursor additives is crucial to achieving high efficiency and stable perovskite quantum dot light‐emitting diodes (Pe‐QLEDs). Herein, a strategy using 4‐dodecylbenzenesulfonic acid (DBSA) is developed to simultaneously suppress halide interstitial and vacancy defects by tuning the crystallization process of perovskite quantum dots (Pe‐QDs) through coordinate bonding and chemical circumstance modulation, leading to faster radiative recombination and less carrier accumulation in the device. Meanwhile, the Pe‐QDs with defect suppression demonstrate higher ion migration activation energies. Thanks to the defect suppression strategy with the aid of the alkyl sulfonic group, the obtained Pe‐QDs exhibit an external quantum efficiency (EQE) of up to 20.4% and an operating lifetime of over 100 h in QLED, which is the leading performance of green Pe‐QLEDs. This work provides a strategy from a different aspect for the perovskite QLED field in improving the performance and stability of devices.
A Strategy for Designing Multifunctional TADF Materials for High‐Performance Non‐doped OLEDs by Intramolecular Halogen Bonding
Authors: Ge Xiangyu , Li Gaoyu , Guo Danman , Yang Zhan , Mao Zhu , Zhao Juan , Chi Zhenguo
Published: December 2023

The development of multifunctional thermally activated delayed fluorescence (TADF) material with high efficiency is indeed a formidable challenge. The difficulty arises from the need to achieve multiple desirable radiation pathways simultaneously during the emission process. In this context, a novel strategy to construct multifunctional emitters with high emission efficiency by modulating intramolecular halogen bonding through structural isomerism is proposed. The designed molecule DMAC‐2FDPS exhibits multifunctional features, including aggregation‐induced emission, mechanochromic luminescence, room temperature phosphorescence, mechanoluminescence, and TADF. Notably, in neat film, DMAC‐2FDPS demonstrates an exceptionally high photoluminescence quantum efficiency of up to 93%. Through single‐crystal analysis and theoretical calculations, it is revealed that the intramolecular halogen bonding in this molecule plays a crucial role in achieving both multifunctional emission and high PLQY. Furthermore, when utilized in non‐doped organic light‐emitting diodes (OLEDs), DMAC‐2FDPS achieves a maximum external quantum efficiency of up to 21.2%. To the best acknowledge, it is almost the highest efficiency for non‐doped OLEDs based on multifunctional materials with five characteristics. These results certify a new strategy for the development of high‐efficiency multifunctional TADF materials and devices.
Color‐Tunable Room Temperature Afterglow of Non‐Conventional Organogels for Dynamic Anti‐Counterfeiting
Authors: Xiang Juanjuan , Shi Yi , Jiang Jiayu , Yan Jiaying , Xiao Shuzhang , Lin Huamiao , Yi Tao
Published: December 2023

Low‐molecular‐weight organogels with ultra‐long room temperature phosphorescent (RTP) are ideal materials for dynamic anti‐counterfeiting, due to their sensitive thermal‐responsive character. However, it is a great challenge to realize ultra‐long RTP in a single‐component organogel because conventional auxiliary groups for the promotion of gel formation are usually flexible, which increases non‐radiative decay through molecular motions to quench the RTP. Non‐conventional organogelators with rigid chemical structures may be able to alleviate the non‐radiative decay to maintain the phosphorescent characters in the gel state like in the crystalline state. In this work, potential low‐molecular weight phosphorescent organogelators with rigid chemical structures are predicted by using the descriptors derived from all‐atom molecular dynamics simulation, and successfully screen out two RTP non‐conventional organogelators. It is exciting that one of them exhibited ultra‐long RTP in the gel state. Furthermore, triplet‐to‐singlet Forster resonance energy transfer between the RTP gelator (donor) and fluorescent sulforhodamine 101 (SR101) (acceptor) in the gel state provided a long‐lived red fluorescence. Due to the sensitive thermal‐responsive property of organogel, the afterglow can be well switched between “on” and “off” with excellent fatigue‐resistant properties, which is promising for dynamic anti‐counterfeiting.
Stereospecific Indium(III)‐Catalysed Tandem Cycloisomerization of Functionalized 1,6‐enynes: Scope and Mechanistic Insights
Authors: Pérez‐Guevara Raquel , Sarandeses Luis A. , Álvarez Rosana , Martínez M. Montserrat , Pérez Sestelo José
Published: December 2023

Tandem cycloisomerization reactions of functionalized 1,6‐enynes under indium(III) catalysis are described. This atom‐economic transformation proceeds smoothly with 5‐exo‐dig regioselectivity using commercial In(III) halides and 1,6‐enynes furnished with alcohol, carboxylic acid or amine functional groups to give bicyclic structures in good yields and diastereoselectivities. The reaction with enynals involves a three–step mechanism to give an oxatricycle and a conjugated 1,3‐diene. In the absence of the internal nucleophile the enyne cycloisomerization evolves through a skeletal rearrangement or a cyclopropanation reaction after the regioselective 5‐exo‐dig cyclization. The 1,6‐enyne cycloisomerization is stereospecific and the stereoselectivity appears to be independent of the internal nucleophile. Experimental data support a common reaction mechanism involving an initial alkyne electrophilic π‐coordination of In(III) followed by Markovnikov electrophilic alkene addition and ring‐closure by nucleophilic attack. DFT studies hold up a stepwise mechanism involving the formation of a chiral non‐classical carbocation intermediate that determines the diastereoselectivity of this tandem cycloisomerization reaction.
CURATE.AI—Artificial Intelligence‐Derived Personalized Tacrolimus Dosing for Pediatric Liver Transplant: A Retrospective Study
Authors: Tan Shi‐Bei , Senthil Kumar Kirthika , Gan Tiffany Rui Xuan , Tan Lester W. J. , Truong Anh T. L. , Blasiak Agata , Aw Marion M. , Mali Vidyadhar Padmakar , Ho Dean
Published: December 2023

Tacrolimus is the cornerstone of immunosuppressive therapy after pediatric liver transplantation. However, reliance on the physician's experience for dose titration, coupled with tacrolimus's narrow therapeutic window and inter‐ and intrapatient variability, often results in frequent under or overdosing events with detrimental patient outcomes. Existing predictive dose personalization models are not readily feasible for clinical implementation, as they require multiple measurements each day while the standard frequency is once daily. CURATE.AI, a small‐data artificial intelligence‐derived platform, is developed as a clinical decision support system to dynamically personalize doses using the patient's own data obtained once a day. Retrospective dose personalization with CURATE.AI on 16 patients’ data demonstrates potential to enable more patients to reach therapeutic range within the first week. The findings support the testing of CURATE.AI in a prospective controlled trial as an aid for the physician's decision on tacrolimus dose personalization after pediatric liver transplantation.
Dual‐Loop Control Design for Dynamic Positioning Ships with Prescribed Performance
Authors: Gong Chenglong , Su Yixin , Li Mingyang , Zhang Danhong , Li Hangbiao
Published: December 2023

Dynamic positioning (DP) system is an advanced positioning system widely used in various special operation ships, and the design of control strategies to cope with different constraint conditions is the core technology of DP system research. In this study, a novel dual‐loop control law is proposed to effectively tackle the control challenges encountered by DP ships, particularly in the presence of input saturation and error constraints. Firstly, a saturation handling model is designed to avoid input saturation in the system. Subsequently, a dual‐loop DP control scheme is developed. The outer‐loop is responsible for the ship's position and heading control, while concurrently providing the command velocity signal essential for the inner‐loop. Specifically, a prescribed performance control strategy is designed in the outer‐loop to ensure precise control over positioning errors within predefined ranges and achieve desirable transient and steady‐state performance. The inner‐loop controls the ship's velocity signal, in which a feedback control law is designed based on Hamilton‐Jacobi‐Issacs (HJI) inequality to estimate generalized faults of the DP system. Finally, the proposed control law is validated through numerical simulations on a 76.2 m supply ship, demonstrating superior transient and steady‐state performance compared to existing methods.
A Strategic Comparison Between Monolayers of WX2N4(X≐Si, Ge) Toward Thermoelectric Performance and Optoelectronic Properties.
Authors: Das Chayan , Alam Mahfooz , Saikia Dibyajyoti , Betal Atanu , Gandi Appala Naidu , Sahu Satyajit
Published: December 2023

New 2D layered materials WX2N4(X≐Si, Ge)1 are suitable for thermoelectric applications for a pretty good value of the figure of merit (ZT). Here, the thermoelectric properties of the 2D monolayer of WX2N4(X≐Si, Ge) using Density Functional Theory (DFT) is investigated combined with Boltzmann Transport Equation (BTE) along with spin‐orbit coupling (SOC). An excellent thermoelectric of 0.91 (0.92 with SOC) is obtained at 900 K for p‐type WGe2N4, and a of 0.81 (0.86 with SOC) is observed for n‐type at the same temperature. Furthermore, the WGe2N4 showed a of more than 0.7 (0.79 with SOC) at room temperature for p‐type. On the other hand, the WSi2N4 showed a comparatively lower at room temperature. However, the value increases significantly at higher temperatures, reaching 0.72 (0.79 with SOC) and 0.71 (0.62 with SOC) for p and n‐type at 900 K, respectively. The electronic band structure is examined and discovered that WSi2N4 and WGe2N4 possess indirect bandgaps (BG) of 2.68 eV (2.57 eV with SOC) and 1.53 eV (1.46 eV with SOC), respectively, according to Heyd‐Scuseria‐Ernzerhof (HSE) approximation. These materials may also be useful in UV and visible range optoelectronic devices because of their strong absorption in the respective regions.
LncRNA LINK‐A Remodels Tissue Inflammatory Microenvironments to Promote Obesity
Authors: Chen Yu , Chen Hui , Wang Ying , Liu Fangzhou , Fan Xiao , Shi Chengyu , Su Xinwan , Tan Manman , Yang Yebin , Lin Bangxing , Lei Kai , Qu Lei , Yang Jiecheng , Zhu Zhipeng , Yuan Zengzhuang , Xie Shanshan , Sun Qinming , Neculai Dante , Liu Wei , Yan Qingfeng , Wang Xiang , Shao Jianzhong , Liu Jian , Lin Aifu
Published: December 2023

High‐fat diet (HFD)‐induced obesity is a crucial risk factor for metabolic syndrome, mainly due to adipose tissue dysfunctions associated with it. However, the underlying mechanism remains unclear. This study has used genetic screening to identify an obesity‐associated human lncRNA LINK‐A as a critical molecule bridging the metabolic microenvironment and energy expenditure in vivo by establishing the HFD‐induced obesity knock‐in (KI) mouse model. Mechanistically, HFD LINK‐A KI mice induce the infiltration of inflammatory factors, including IL‐1β and CXCL16, through the LINK‐A/HB‐EGF/HIF1α feedback loop axis in a self‐amplified manner, thereby promoting the adipose tissue microenvironment remodeling and adaptive thermogenesis disorder, ultimately leading to obesity and insulin resistance. Notably, LINK‐A expression is positively correlated with inflammatory factor expression in individuals who are overweight. Of note, targeting LINK‐A via nucleic acid drug antisense oligonucleotides (ASO) attenuate HFD‐induced obesity and metabolic syndrome, pointing out LINK‐A as a valuable and effective therapeutic target for treating HFD‐induced obesity. Briefly, the results reveale the roles of lncRNAs (such as LINK‐A) in remodeling tissue inflammatory microenvironments to promote HFD‐induced obesity.
Design of Polymer Carriers for Optimized Pheromone Release in Sustainable Insect Control Strategies
Authors: Hellmann Christoph , Greiner Andreas , Vilcinskas Andreas
Published: December 2023

Semiochemicals such as pheromones play a major role in communication between insects, influencing their spatial orientation, aggregation, defense, and mating. The rational chemical design of precision pheromone‐releasing materials are increased the efficiency of pheromone‐based plant protection agents. Decades of research is begun to unravel the complex communication structures regulated by semiochemicals, from the neuronal perception of specific chemical substances to the behavioral responses in hundreds of species, including many devastating pest insects. This article summarizes the most effective uses of semiochemicals in agriculture, the behavioral responses of selected target species, and controlled‐release strategies based on formulations such as novel fibrous polymer carriers. This study helps scientists, decision‐makers, farmers, and the public understand the importance of appropriate mating disruption techniques that reduce the need for broad‐spectrum insecticides and limit their impact on non‐target and beneficial insects.
Enhancing Composite Toughness Through Hierarchical Interphase Formation
Authors: Gupta Sumit , Sohail Tanvir , Checa Marti , Rohewal Sargun S. , Toomey Michael D. , Kanbargi Nihal , Damron Joshua T. , Collins Liam , Kearney Logan T. , Naskar Amit K. , Bowland Christopher C.
Published: December 2023

High strength and ductility are highly desired in fiber‐reinforced composites, yet achieving both simultaneously remains elusive. A hierarchical architecture is developed utilizing high aspect ratio chemically transformable thermoplastic nanofibers that form covalent bonding with the matrix to toughen the fiber‐matrix interphase. The nanoscale fibers are electrospun on the micrometer‐scale reinforcing carbon fiber, creating a physically intertwined, randomly oriented scaffold. Unlike conventional covalent bonding of matrix molecules with reinforcing fibers, here, the nanofiber scaffold is utilized ‒ interacting non‐covalently with core fiber but bridging covalently with polymer matrix ‒ to create a high volume fraction of immobilized matrix or interphase around core reinforcing elements. This mechanism enables efficient fiber‐matrix stress transfer and enhances composite toughness. Molecular dynamics simulation reveals enhancement of the fiber‐matrix adhesion facilitated by nanofiber‐aided hierarchical bonding with the matrix. The elastic modulus contours of interphase regions obtained from atomic force microscopy clearly indicate the formation of stiffer interphase. These nanoengineered composites exhibit a ≈60% and ≈100% improved in‐plane shear strength and toughness, respectively. This approach opens a new avenue for manufacturing toughened high‐performance composites.
The Challenge of Superhydrophobicity: Environmentally Facilitated Cassie–Wenzel Transitions and Structural Design
Authors: Zhong Xin , Xie Shangzhen , Guo Zhiguang
Published: December 2023

Superhydrophobic materials can be used in various fields to optimize production and life due to their unique surface wetting properties. However, under certain pressure and perturbation conditions, the droplets deposited on superhydrophobic materials are prone to change from Cassie state to Wenzel state, which limits the practical applications of the materials. In recent years, a large number of works have investigated the transition behavior, transition mechanism, and influencing factors of the wetting transition that occurs when a superhydrophobic surface is under a series of external environments. Based on these works, in this paper, the phenomenon and kinetic behavior of the destruction of the Cassie state and the mechanism of the wetting transition are systematically summarized under external conditions that promote the wetting transition on the material surface, including pressure, impact, evaporation, vibration, and electric wetting. In addition, superhydrophobic surface morphology has been shown to directly affect the duration of the Cassie state. Based on the published work the effects of specific morphology on the Cassie state, including structural size, structural shape, and structural level, are summarized in this paper from theoretical analyses and experimental data.
Multiplexed Surface Electrode Arrays Based on Metal Oxide Thin‐Film Electronics for High‐Resolution Cortical Mapping
Authors: Londoño‐Ramírez Horacio , Huang Xiaohua , Cools Jordi , Chrzanowska Anna , Brunner Clément , Ballini Marco , Hoffman Luis , Steudel Soeren , Rolin Cédric , Mora Lopez Carolina , Genoe Jan , Haesler Sebastian
Published: December 2023

Electrode grids are used in neuroscience research and clinical practice to record electrical activity from the surface of the brain. However, existing passive electrocorticography (ECoG) technologies are unable to offer both high spatial resolution and wide cortical coverage, while ensuring a compact acquisition system. The electrode count and density are restricted by the fact that each electrode must be individually wired. This work presents an active micro‐electrocorticography (µECoG) implant that tackles this limitation by incorporating metal oxide thin‐film transistors (TFTs) into a flexible electrode array, allowing to address multiple electrodes through a single shared readout line. By combining the array with an incremental‐ΔΣ readout integrated circuit (ROIC), the system is capable of recording from up to 256 electrodes virtually simultaneously, thanks to the implemented 16:1 time‐division multiplexing scheme, offering lower noise levels than existing active µECoG arrays. In vivo validation is demonstrated acutely in mice by recording spontaneous activity and somatosensory evoked potentials over a cortical surface of ≈8×8 mm2. The proposed neural interface overcomes the wiring bottleneck limiting ECoG arrays, holding promise as a powerful tool for improved mapping of the cerebral cortex and as an enabling technology for future brain‐machine interfaces.
The Effect of Electrolyte Composition on the Performance of a Single‐Cell Iron–Chromium Flow Battery
Authors: Mans Nico , Krieg Henning M. , van der Westhuizen Derik J.
Published: December 2023

Flow batteries are promising for large‐scale energy storage in intermittent renewable energy technologies. While the iron–chromium redox flow battery (ICRFB) is a low‐cost flow battery, it has a lower storage capacity and a higher capacity decay rate than the all‐vanadium RFB. Herein, the effect of electrolyte composition (active species and supporting electrolyte concentrations), Fe/Cr molar ratio, and supporting electrolyte type (HCl and H2SO4) on the performance (current efficiency (CE), voltage efficiency (VE), energy efficiency, discharge capacity, and capacity decay) of an ICRFB is investigated. The storage capacity of the optimum electrolyte (1.3 m FeCl2, 1.4 m CrCl3, 5.0 mm Bi2O3 in 1.0 m HCl) is 40% higher (from 17.5 to 24.4 Ah L−1), while the capacity decay rate is tenfold lower (from 3.0 to 0.3% h−1) than the performance of the previously used 1.0 m FeCl2, 1.0 m CrCl3 in 3.0 m HCl. At the optimum Fe and Cr concentrations and ratio in 0.5 m HCl, a near constant CE (92.3%), VE (78.7%), and EE (72.6%) are obtained over 50 cycles. The significantly higher capacity decay when using 1.0 m H2SO4 (1.6% h−1) compared to 1.0 m HCl (0.3% h−1) confirms that HCl is the more suitable supporting electrolyte.
The ability to inhibit impulses is related to social behavior in long‐tailed macaques
Authors: Overduin‐de Vries Anne M. , Vermande Marjolijn M. , Hessen David J. , Sterck Elisabeth H. M.
Published: December 2023

Performance in cognitive tasks has been linked to differences in species' social organization, yet to understand its function its relationship to within‐species variation in behavior should also be explored. One important cognitive capacity, the ability to inhibit impulses, is typically better in egalitarian than despotic primate species and in primate species with strong fission‐fusion dynamics. A different line of research indicates that a high ability to inhibit impulses is related to less aggressive behavior and more socio‐positive behavior. However, within species the relationship between performance on cognitive inhibition tasks and variation in social behavior remains to be explored. Here we investigate how performance in a typical inhibition task in cognitive research is related to aggressive and socio‐positive behavior in despotic long‐tailed macaques. Twenty individuals living in two naturalistic mixed‐sex groups were tested with the Plexiglass Hole Task. Aggressive behavior and three types of socio‐positive behavior (neutral/friendly approaches, socio‐positive signaling, and grooming others) among group members were measured. Individuals differed in their ability to inhibit impulses. Individuals that were not good at inhibiting impulses showed higher rates of aggressive behavior, but also more socio‐positive signals, whereas inhibition was not related to neutral/friendly approaches and grooming. These results confirm the positive link between impulsiveness and aggression. In addition, the results indicate that some social‐positive behavior may be enhanced when inhibition is limited. In this species, benefits potentially derived from aggression and socio‐positive signals match a low ability to inhibit impulses, suggesting that a low ability to inhibit impulses may actually be advantageous. To understand differences between species in cognitive skills, understanding the benefits of variation in a cognitive capacity within a species is crucial.
Tracking plasma biomarkers in cognitively unimpaired individuals at risk of Alzheimer’s disease
Authors: Suarez‐Calvet Marc
Published: December 2023

Alzheimer’s disease (AD) is as a continuum that includes a preclinical phase, where individuals are cognitively unimpaired but there is evidence of amyloid‐β (Aβ) and tau pathology, followed by a clinical phase (including mild cognitive impairment and dementia). This preclinical phase is not a uniform or unvarying phase, but it is a long process during which Aβ and tau gradually accumulates until overt Aβ plaque deposition and neurofibrillary tangles are present. Moreover, this is a heterogeneous phase, there are differences in the rate of progression of those individuals that are Aβ‐positive to cognitive impairment and some of them will not even develop symptoms. It is important to develop biomarkers that accurately detect Preclinical AD, but also biomarkers to stage the disease, and prognostic biomarkers that identify those individuals that will progress to cognitive impairment. Furthermore, amid the new developments of disease modifying treatments, there is an unmet need to develop biomarkers to predict and monitor the response to an intervention.

We now have a range of plasma biomarkers that detect symptomatic AD but also increase in Preclinical AD, including several epitopes of p‐tau (pT181, pT217, pT231), Aβ42/40, GFAP and NfL. Yet, there are differences between them. They may differ on which point of the long preclinical stage they start to increase, their discrimination accuracy, their longitudinal changes across the disease continuum or the physiopathological mechanism that they indicate. Moreover, the performance of plasma biomarkers may be influenced by sex and gender, race and ethnicity, or comorbidities. Therefore, the choice of the plasma biomarker may differ depending on its goal.

In this presentation, plasma biomarkers in Preclinical AD will be reviewed and their differential roles will be discussed.
Towards implementation of neurofilament light in clinical practice
Authors: Vermunt Lisa
Published: December 2023

Discussion of recent advances and approaches to the implementation of the Neurofilament light chain laboratory test in clinical practice for cognitive disorders and in the broader neurology and medical field.
Neuropathological hallmarks in the eye: towards biomarkers for neurodegeneration
Authors: Hoozemans Jeroen
Published: December 2023

The retina, an extension of the central nervous system, has emerged as a valuable tool for the study of neurodegeneration, as it shares many structural and functional features with the brain. The retina is easily accessible and can be examined non‐invasively, making it an attractive target for the development of biomarkers for neurodegenerative diseases. Several neuropathological hallmarks have been identified in the retina that are associated with neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and frontotemporal lobar degeneration (FTLD). The identification of specific biomarkers in the retina may aid in the early detection and diagnosis of neurodegenerative diseases, as well as in the monitoring of disease progression and treatment efficacy.

In order to progress these findings into reliable biomarkers, various aspects in this field require attention. Access to post mortem retina tissue, together with characterized brain tissue samples, is essential for the study of retinal pathology in relation to brain pathology. This will allow for the examination of the relationship between retinal and brain pathology and may provide important insights into the mechanisms underlying neurodegeneration. In addition, the assessment of retinal pathology requires standardized approaches, as there is currently no consensus on the methods used to evaluate retinal tissue. Standardized approaches are necessary to ensure the accuracy and reproducibility of results, as well as to facilitate comparison between different studies. Artificial intelligence (AI) has the potential to revolutionize the field of retinal pathology, as it can facilitate the identification of subtle changes in retinal structure that may be indicative of neurodegenerative disease.

In conclusion, the retina has emerged as a valuable tool for the study of neurodegeneration. The identification of neuropathological hallmarks in the retina, increased understanding of retinal pathology in relation to brain pathology, standardized approaches for the assessment of pathology, access to post mortem retina tissue, and the use of AI all have the potential to advance the field of retinal pathology and aid in the development of biomarkers for neurodegenerative diseases.
Human postmortem studies as a driver of model development
Authors: Nguyen Aivi T.
Published: December 2023

The neuroimmune response in human aging and Alzheimer’s disease (AD) is complex and heterogeneous. Numerous genome wide associated studies have shown several AD genetic risk loci related to innate immunity and microglial function, of which APOE E4 and TREM2 R47H have been shown to influence microglial activation states. Microglial heterogeneity, characterized by morphology and function, has long been documented in human and murine literature. Using single‐nuclei RNA sequencing, one distinct reactive microglial subpopulation termed amyloid‐responsive microglia (ARM) was previously characterized in postmortem human AD brain tissue harboring various genetic risk variants, including APOE E4 and TREM2 R47H, and further validated in an expanded autopsy cohort using an immunohistochemical (IHC) marker for ARM. Herein described is an abbreviated study exploring the clinical utility of postmortem ARM IHC and its potential relationship to antemortem biomarkers, such as fluid and neuroimaging biomarkers, and cognition. Also discussed is the integration of digital pathology and artificial intelligence (AI)‐based algorithms to translate postmortem microglial findings into potential research application and model development.
Lessons from neuropathology to inform on fluid biomarkers of amyloid and tau
Authors: Mattsson‐Carlgren Niklas
Published: December 2023

Fluid biomarkers of amyloid and tau, including measures in both cerebrospinal fluid and plasma, have been used extensively in clinical and translational studies of Alzheimer’s disease and other neurodegenerative diseases. These biomarkers are now also increasingly used in clinical practice to inform on diagnosis and prognosis. Despite a successful development of new biomarkers with high diagnostic accuracy for Alzheimer’s disease, the exact relationship between fluid biomarkers and underlying pathological changes in the brain of patients with neurodegenerative diseases have long been unclear.

Multimodal studies that integrate state‐of‐the‐art fluid biomarkers with neuropathological measurements are now beginning to inform on the exact relationship between alterations in soluble protein levels and underlying pathological changes. These findings have broad implications for the optimal use of fluid amyloid and tau biomarkers in clinical practice, research, and development of drugs targeting specific neuropathological mechanisms.

This talk will highlight recent key findings in this field, discuss remaining challenges, and point out future directions for research.
Racial/Ethnic Disparities in the Alzheimer’s Disease Link with Cardiovascular Disease, based on Hawaii Medicare Population
Authors: Siriwardhana Chathura
Published: December 2023

Background

There is an expanding body of literature implicating heart disease and stroke as risk factors for Alzheimer’s disease (AD). Hawaii has the most diverse ethnic population in the US and there exist racial health disparities. E.g., Native‐Hawaiians/Pacific‐Islanders (NHPI) are well‐known as a high‐risk group for a variety of conditions. In this study, we explored the association of heart disease and stroke on AD development, focusing on racial disparities.

Method

We utilized nine years of Hawaii Medicare data to gather information on developing heart failure (HF), ischemic heart disease (IHD), atrial fibrillation (AF), acute myocardial infarction (AMI), stroke, and progression to AD, followed by multistate models. Propensity score‐matched control groups without heart disease or stroke were identified to compare the risk of AD after heart disease and stroke. Racial effects were tested on progression to AD, accounting for risk factors

Result

We found increased risk of developing AD for AF (Relative Risk [RR] = 1.09, p<0.001), HF (RR = 1.21, p<0.001), IHD (RR = 1.17, p<0.001), stroke (RR = 1.15, p<0.001) and a borderline significance for the AMI (RR = 1.09, p = 0.073), compared to whites. Socioeconomic status given by the Medicare/Medicaid dual eligibility status was found to be a critical factor in AD risk and regulating racial effects. Among the individuals with a poor socio‐economic background (dual eligible), increased AD risk found for NHPIs compared to whites, from HF (RR = 1.32, p = 0.046), IHD (RR = 1.37, p = 0.004), and stroke (RR = 1.41, p = 0.025), after adjustment for multiple covariates. NHPIs had consistently increased AD risks compared to Asians from all five states: AF (RR = 1.54, p = 0.004), AMI (RR = 1.72, p = 0.024), HF (RR = 2.23, p<0.001), IHD (RR = 2.39, p<0.001), and stroke (RR = 1.85, p<0.001). Interestingly, these relationships found to be different in the Medicare‐only group, in which reduced AD risks found in NHPIs compared to whites for many conditions, including AF (RR = 0.70, p = 0.037), HF (RR = 0.54, p = 0.006), and IHD (RR = 0.75, p = 0.034). NHPIs also had reduced risk compared to Asians from HF (RR = 0.73, p<0.001) and IHD (RR = 0.58, p<0.001) to AD transition.

Conclusion

The risk of developing AD is high among heart disease and stroke patients, and it is varied among races.
Graph Theory Analysis of Structural Connectivity in Limbic‐predominant Age‐related TDP‐43 Encephalopathy Neuropathological Change (LATE‐NC)
Authors: Tazwar Mahir , Evia Arnold M , Ridwan Abdur Raquib , Bennett David A. A , Schneider Julie A , Arfanakis Konstantinos
Published: December 2023

Background

The anatomical distribution of limbic‐predominant age‐related TDP‐43 encephalopathy neuropathological change (LATE‐NC) typically involves the amygdala, hippocampus, and other subcortical, temporal and frontal lobe regions. But its impact on the structural integrity of this network of regions remains unknown. In this study, we tested the hypothesis that LATE‐NC is associated with abnormalities in graph theoretic measures of structural connectivity in the network of regions known to be involved in LATE‐NC.

Method

This study included 148 deceased older adults participating in Rush Memory and Aging Project and Religious Orders Study (Fig.1A). Ex‐vivo diffusion tensor imaging (DTI) scans were acquired on 3T scanners, followed by detailed neuropathologic examination by a board‐certified neuropathologist (Fig.1B). Fractional anisotropy (FA) maps derived from DTI scans were used to define region‐to‐region structural connectivity in a network of 19 regions known to be involved in LATE‐NC using graph theory‐based network measures (Fig.2).

General linear models were used to investigate the association of global and local graph measures with LATE‐NC stages, controlling for other neuropathologies (Alzheimer’s disease, Lewy bodies, arteriolosclerosis, atherosclerosis, cerebral amyloid angiopathy, gross and microscopic infarcts), demographics (age at death, sex, education), total white matter hyperintensity volume, postmortem intervals and scanner variables. Statistical significance was set at p<0.05.

Result

Linear regression revealed that greater LATE‐NC stage was associated with increased characteristic path length and with lower values of the remaining global network measures (p<0.05) (Fig.3A). LATE‐NC was also associated with lower local efficiency, increased path length, lower nodal strength, and lower clustering coefficient in 74%, 79%, 32%, and 63% of the nodes, respectively (p<0.05) (Fig.3B). Finally, LATE‐NC was associated with both greater (in 21% of nodes) and lower (in 16% of nodes) eigenvector centrality, and with both greater and lower betweenness centrality in 21% of nodes, respectively (p<0.05) (Fig.3B).

Conclusion

Using graph theory and a hypothesis‐driven approach, we found significant degradation of structural integrity in white matter of the network of regions affected by LATE‐NC. These findings may shed light on the effects of LATE‐NC on brain connectivity, and in combination with other imaging and clinical information, may aid towards the development of tools for in‐vivo detection of this devastating neuropathology.
MRI reveals cerebral iron, calcification and spinal cord atrophy in M83 mouse model of Parkinson’s disease
Authors: Tournant Agathe , Combes Benjamin F. , Law Man Hoi , Antunes Ines , Dias Santos , Noain Daniela , Klohs Jan , Baumann Christian R. , Razansky Daniel , Nitsch Roger M. , Ni Ruiqing
Published: December 2023

Background

Rodent models of Parkinson’s disease have been crucial tools for understanding the pathogenic mechanisms of alpha‐synuclein‐associated alterations. Here, we employed multiparametric high‐field magnetic resonance imaging (MRI) to examine the molecular alterations and neurodegeneration in the brain and spinal cord of transgenic M83 (A53T) murine model of Parkinson’s disease.

Method

Ten nontransgenic littermates and twelve M83 mice at 10‐11 months of age were assessed. Gradient echo MR for susceptibility‐weighted imaging (SWI) and T1 MR scans were acquired ex vivo at 9.4 T in the brain and spinal cord of mice. Histology and immunofluorescence staining for alpha‐synuclein inclusions (phospho‐S129), NeuN, GFAP and Iba‐1 for gliosis were used to investigate the nature of the imaging observations.

Result

From T1 MR, a reduced area of white matter in the thoracic spinal cord (T1) and a reduced area of gray matter in the cervical (C6‐C8) and thoracic (T1) spinal cord were observed in the M83 mice compared to nontransgenic mice. In addition, lower left‐right length measurements in the cervical (C8) spinal cord were observed in M83 mice than in nontransgenic mice. SW images revealed regional hypointensities in the hippocampus, cortex, striatum, midbrain and thalamus of M83 mice, which in corresponding phase images indicated both diamagnetic (calcification) and paramagnetic (iron) lesions in the brains of M83 mice. Immunofluorescence staining demonstrated an increased Iba‐1 level in the brains of M83 mice, indicating microgliosis.

Conclusion

We found cerebral iron, calcification, microgliosis and spinal cord atrophy in M83 mice.
DemenTitude® ‐ Applying the Concept of “LAN” with 16‐grid Dementia Care Model through the Voice of People with Dementia
Authors: Chui Kenny Chi Man
Published: December 2023

Understanding the self‐perception of people with dementia and their interaction with the surrounding others is highly vital to exploring the unmet needs of people with dementia. In preserving the personhood through the person‐centred care approach, the synchronization with the experience of the person with dementia and listening to his/her voice of interpreting the surrounding things should be promoted. What is the meaning of the dialogues and the behavior of people with dementia? How can the “LAN” with 16‐grid dementia care model be applied to guide the care providers and the care partners in maintaining a good quality of care? In‐depth interviews and participatory observations were conducted during interviews in the community care and residential care homes of Hong Kong. Following the theoretical framework blending interpretivism and the sociocultural perspective on dementia, the finding was not only being used for getting more familiar with the experience of people with dementia but also designing the content of educational programme to the care providers and the care partners in Hong Kong.

“LAN” model stands for “L‐listening to the experience and voice of people with dementia; A‐assess the condition of people with dementia through person‐centred care approach; N‐Needs of people with dementia to preserve personhood”. As the care providers and the care partners are trying to synchronize the experience of people with dementia, the subjective views and feeling of people with dementia formed by their interpretation will be the key to respond their unmet needs. A particular educational programme with 16‐grid of dementia care model was designed for the care providers and care partners. Focusing on the synchronization of the experience of people with dementia with LAN model, the participants got reflection and insights on this idea. In satisfying the needs of people with dementia, the participant should learn from the lens of people with dementia and VIPS approach. A proper caring attitude with this “LAN” model, called as DemenTitude®, was introduced. The evaluation of the educational training showed a significant improvement in the positive perception of dementia among the participants.
Thematic Analysis of How Scientists Are Perceived in Newspaper Articles About Contested Science and in the Associated Comments Sections
Authors: Donois Katrine Kergrohen
Published: December 2023

Background

In recent years, societal polarization over contested science has reached worrisome levels despite receiving much attention from researchers working in different fields spanning from neuroscience to journalism. In an attempt to understand the dynamics of polarization, much research focuses on media discourse. However, the newspapers’ comment sections (in which readers react) remain unexplored Thus, this study differs in that it argues that though the media may tell us what to think about, online commentators are telling us how to think about it.

Method

Reflexive thematic analysis was used to identify themes in 84 articles (all mentioning contested science of climate change, GMOs, or vaccines) and the associated comments sections (a total of 25.121 comments).

Result

Four themes were identified, and they suggest that there are commonalities or patterns in the discourse surrounding contested science topics and in how scientists (or experts) are perceived across different fields. Understanding this pattern will help guide future communication strategies.

Conclusion

Scientists are used by those for or against GMOs, vaccination, or climate change. For example, expert knowledge is drawn upon to strengthen, support, and serve as evidence for claims by journalists and commentators. However, people who distrust experts are not all advocates for misinformation or conspiracy theorists; some have (what they express as) legitimate grievances and worries. This study suggests ways for experts to improve science communication by taking the latter into account.
A comparison of word‐list and story recall tests for prediction of biomarker‐determined Alzheimer’s disease
Authors: Bruno Davide , Zinkunegi Ainara Jauregi , Kollmorgen Gwendlyn , Carboni Margherita , Wild Norbert , Carlsson Cynthia M. , Bendlin Barbara B , Okonkwo Ozioma , Chin Nathaniel A. , Hermann Bruce P , Asthana Sanjay , Zetterberg Henrik , Blennow Kaj , Langhough Rebecca E , Johnson Sterling C , Mueller Kimberly D
Published: December 2023

Background

Word‐list and story recall tests are routinely employed in clinical practice for dementia screening. Previous research has shown that both types of tests are predictive of subsequent clinical diagnoses of dementia, including when examining process scores such as forgetting rate. In this study, our aim was to establish how well standard clinical metrics compared to process scores derived from word‐list and story recall tests in predicting biomarker‐determined Alzheimer’s disease (bdAD), as defined by CSF p‐tau/Abeta42 ratio.

Method

Data from 381 participants (mean age = 65, ± 9) were drawn from the University of Wisconsin – Madison Alzheimer’s Disease Research Center (ADRC) and Wisconsin Registry for Alzheimer’s Prevention (WRAP). Rey’s Auditory Verbal Learning Test (AVLT; word‐list) and Logical Memory Test (LMT; story) data were available. The conventional clinical scores examined were: AVLT total recall, AVLT delayed recall, LMT immediate recall, and LMT delayed recall. The process scores examined were: AVLT recency ratio (i.e., recency forgetting), AVLT total forgetting, LMT recency ratio, LMT total forgetting, and LMT primacy ratio (i.e., primacy forgetting). Bayesian linear regression analyses were carried out with either the nearest or farthest CSF p‐tau/Abeta42 ratio as outcome; the standard and process baseline memory scores as predictors; and baseline age, time elapsed from baseline to lumbar puncture, APOE risk score, sex, and years of education as control variables. Sensitivity analyses were carried out with logistic regressions using a cut‐off of 0.038 CSF p‐tau/Abeta42 ratio as outcome, to assess diagnosticity. CSF biomarkers were measured using the NeuroToolKit (Roche Diagnostics International Ltd, Rotkreuz, Switzerland).

Result

LMT recency ratio and LMT primacy ratio were the best performing predictors (BF10 > 1 billion) both when evaluating the nearest (Figure 1a) and the farthest (Figure 1b) outcomes. However, sensitivity analyses with a binary cut‐off favored the primacy ratio. Areas under the curve (AUCs) ranged from 0.86 to 0.87 (including covariates). Specificity was consistently high for primacy ratio with 94% probability of correctly identifying individuals without bdAD.

Conclusion

Our study shows that story recall tests may be better than word‐list tests for dementia screening, especially when employing process scores alongside conventional clinical scores.
Decline in proper name retrieval during story recall is associated with Alzheimer’s disease CSF biomarkers in cognitively unimpaired individuals
Authors: Mueller Kimberly D , Soldan Anja , Langhough Rebecca E , Basche Kristin E , Hale Madeline R , Sanson‐Miles Leah , Moghekar Abhay , Albert Marilyn S. , Pettigrew Corinne
Published: December 2023

Background

Remembering names of people and places is a common problem in aging that is exacerbated in Alzheimer’s disease (AD). Because retrieval of proper names (PNs) has been associated with brain regions affected by AD (anterior and medial temporal lobe), PN retrieval may be an especially sensitive measure of early AD pathology. Extending results of a previous study from WRAP (Mueller et al., 2020), this study examined associations between cerebrospinal fluid (CSF) AD biomarkers and longitudinal delayed story recall PN retrieval.

Method

Participants were from the BIOCARD study, a cohort of late‐middle aged adults enriched for parental history of AD. Participants were cognitively unimpaired at baseline with longitudinal item‐level data from the Logical Memory (LM; WMS‐R) Story A recall (N = 218; M(SD) baseline age = 58(9); M(SD) follow‐up = 4.1(2.9) years). CSF amyloid beta (Ab42/40) and phosphorylated tau181 (p‐tau181) were measured using automated electrochemiluminescence assays; AD biomarker abnormality (+) was determined using the bottom quartile for Ab42/40 and the top quartile for p‐tau181. We calculated total Story A PNs (range 0‐4) and total score (0‐25). We performed longitudinal linear mixed effects (LME) models examining the interaction between time (LM age, centered) and last available Ab42/40 and/or p‐tau181 status as predictors of PNs and total recall (subject‐specific random intercepts).

Result

Of the 218 participants included, forty‐nine (22.4%) were Ab42/40+, 60 (27.5%) were p‐tau181+, and the remainder were A‐/T‐ (Table 1). In LME models, CSF‐Ab42/40+*age was not a significant predictor of either outcome. The p‐tau181+*age interaction showed significantly greater annual decline in PNs in the p‐tau181+ group than the p‐tau181‐ group (interaction beta = ‐.01, p = .02; simple slope estimate p‐tau181‐ = .002, p‐tau181+ = ‐.01) (Table 2, Fig.1). Interaction patterns were weaker yet similar for total recall. In follow‐up analyses, 15 participants who converted to MCI or dementia were removed and results remained unchanged. In an exploratory model combining biomarker statuses, the Ab42/40+/p‐tau181+*age interaction was non‐significant.

Conclusion

As in the WRAP study, these results from BIOCARD indicate that PN recall is more sensitive to preclinical change than the traditional story recall total score metric; results also indicate that decline is greatest in those with elevated CSF p‐tau. Future directions should include replication in other longitudinal cohorts.