bluuebunny/crossref_metadata_2025 huggingface dataset:
Optically Controlled Latching and Launching in Soft Actuators
Authors: Guo Hongshuang , Priimagi Arri , Zeng Hao
Published: December 2021

Snapping is an abrupt reaction, in which mechanical instability allows the structure to rapidly switch from one stabilized form to another. Snapping is attained through a sudden release of prestored elastic energy. It is perfected by natural species to enhance their preying, locomotion, and reproduction abilities. Recent developments in responsive materials research has allowed the realization of bioinspired snappers and rapidly moving soft robots triggered by external stimuli. However, it remains a grand challenge to reversibly and accurately control the snapping dynamics in terms of, e.g., onset timing and speed of motion. Here, a facile method to obtain light‐fueled snapping‐like launching with precise control over the elastic energy released and the onset timing is reported. The elastic energy is prestored in a light‐responsive liquid crystal elastomer actuator, and the launching event is dictated by releasing the energy through a photothermally induced crystal‐to‐liquid transition of a liquid‐crystalline adhesive latch. The method provides manual control over the amount of prestored energy, motion speed upon multiple launching events, and enables demonstrations such as jumping and catapult motions in soft robots and concerted motions of multiple launchers. The results provide a practical solution for controlled fast motions in soft small‐scale robotics.
Confinement Effects in Individual Carbon Encapsulated Nonprecious Metal‐Based Electrocatalysts
Authors: Shen Ling , Ying Jie , Ozoemena Kenneth I. , Janiak Christoph , Yang Xiao‐Yu
Published: December 2021

The evolution of cost‐effective and reserve‐rich nonprecious metals (NPMs) to replace precious metal electrocatalysts is of significant interest in modern electrocatalysis. The confinement effects in NPM‐based nanoparticles encapsulated in carbon nanoshells have been considered as an emerging and efficient way to special types of electrocatalysts which facilitate electrocatalytic activity and stability, even under rigorous conditions. This review focuses on the unique individual carbon encapsulation for high‐performance design of NPM‐based electrocatalysts, outlining all confinement synthesis methods, mechanistic studies on confinement effects, and the emerging practical reactions. It begins first introducing the synthetic methods for NPM‐based core@carbon shell electrocatalysts, and then follows clarification of the relationship between the fundamental confinement effects and the performance improvement of carbon shell encapsulating NPM‐based electrocatalysts. Further and detailed discussions on the alloying effect, doping effect, and heterojunction effect of the NPM‐based core to alter the electronic situation which affects the electrocatalytic performance are subsequently provided. Finally, the review provides a perspective on challenges and opportunities in future research with respect to both in‐depth theoretical research and potential design concept of such NPM‐based core@carbon shell electrocatalysts.
Mimicking Native Heart Tissue Physiology and Pathology in Silk Fibroin Constructs through a Perfusion‐Based Dynamic Mechanical Stimulation Microdevice
Authors: Mehrotra Shreya , de Melo Bruna Alice Gomes , Miscuglio Mario , Kiaee Kiavash , Shin Su Ryon , Mandal Biman B.
Published: December 2021

In vitro cardiomyocyte (CM) maturation is an imperative step to replicate native heart tissue‐like structures as cardiac tissue grafts or as drug screening platforms. CMs are known to interpret biophysical cues such as stiffness, topography, external mechanical stimulation or dynamic perfusion load through mechanotransduction and change their behavior, organization, and maturation. In this regard, a silk‐based cardiac tissue (CT) coupled with a dynamic perfusion‐based mechanical stimulation platform (DMM) for achieving maturation and functionality in vitro is tried to be delivered. Silk fibroin (SF) is used to fabricate lamellar scaffolds to provide native tissue‐like anisotropic architecture and is found to be nonimmunogenic and biocompatible allowing cardiomyocyte attachment and growth in vitro. Further, the scaffolds display excellent mechanical properties by their ability to undergo cyclic compressions without any deformation when places in the DMM. Gradient compression strains (5% to 20%), mimicking the native physiological and pathological conditions, are applied to the cardiomyocyte culture seeded on lamellar silk scaffolds in the DMM. A strain‐dependent difference in cardiomyocyte maturation, gene expression, sarcomere elongation, and extracellular matrix formation is observed. These silk‐based CTs matured in the DMM can open up several avenues toward the development of host‐specific grafts and in vitro models for drug screening.
Aqueous Aluminum‐Carbon Rechargeable Batteries
Authors: Smajic Jasmin , Hasanov Bashir E. , Alazmi Amira , Emwas Abdul‐Hamid , Wehbe Nimer , Genovese Alessandro , El Labban Abdulrahman , Costa Pedro M. F. J.
Published: December 2021

Carbon cathodes have shown excellent electrochemical behavior in aluminum batteries based on non‐aqueous electrolytes. By contrast, their use in Al systems operating in a salt‐water medium is plagued by poor and unstable performance. Herein, it is sustained that a successful C cathode for rechargeable aqueous Al batteries requires surface customization to enable hydrophilicity and grafting of charged Al molecules. Employing a freeze‐dried reduced graphene oxide (rGO) as the active electrode material, an aqueous Al‐C battery is assembled with a high energy density (136 Wh kg−1 per cathode mass) and one of the best capacity retentions reported (≈60% across a range of current densities and constant Coulombic efficiencies close to unit). Furthermore, the rGO cathode more than doubles the benchmark for life cycles (to ≈200 cycles) and can be charged rapidly (<5 min). To explain this response, a charge storage mechanism is proposed wherein the [Al(H2O)6]3+ ions do not get desolvated when inserted into the cathode. The guest Al ions (surface adsorbed or intercalated) act as proton donors and may get anchored on the oxygen moieties of the rGO, further promoting the formation of an electrochemical double layer. A mixed charge‐storage regime follows that stabilizes the carbon cathode and enables an unprecedented response.
Small‐Sized Deformable Shear Sensor Array for Direct Monitoring of Quantitative Shear Distribution
Authors: Suh Wonjeong , Park Chaeyong , Oh Joosung , Moon Sungmin , Choi Seungmoon , Kim Youn Soo , Jeong Unyong
Published: December 2021

An array of shear sensors is essential in tactile sensation as well as the pressure sensors. Surprisingly, however, the shear sensor array is rarely investigated mainly due to the structural complexity to measure the horizontal forces from various directions and also due to the mechanical softness required for preventing the slip of an object. Here, an array of small shear sensors that can recognize both shear force and shear rotational angle is fabricated. All the device components are made of deformable materials to acquire the softness of the sensor. This work presents a novel design for the small‐sized shear sensor array and the required material conditions for the design. By using an ion gel as the capacitive sensing material, the shear sensor array shows high sensitivity and excellent reliability under repeated shear forces. This work demonstrates playing computer game with the shear sensor and sensing the frictional force distribution, which is possible through the recognition of multiple shear stimuli and spatial shear distribution (force, rotational angle) when static/dynamic shear forces are simultaneously applied from various directions.
Martini 3 Coarse‐Grained Force Field: Small Molecules
Authors: Alessandri Riccardo , Barnoud Jonathan , Gertsen Anders S. , Patmanidis Ilias , de Vries Alex H. , Souza Paulo C. T. , Marrink Siewert J.
Published: December 2021

The recent re‐parametrization of the Martini coarse‐grained force field, Martini 3, improved the accuracy of the model in predicting molecular packing and interactions in molecular dynamics simulations. Here, we describe how small molecules can be accurately parametrized within the Martini 3 framework and present a database of validated small molecule models. We pay particular attention to the description of aliphatic and aromatic ring‐like structures, which are ubiquitous in small molecules such as solvents and drugs or in building blocks constituting macromolecules such as proteins and synthetic polymers. In Martini 3, ring‐like structures are described by models that use higher resolution coarse‐grained particles (small and tiny particles). As such, the present database constitutes one of the cornerstones of the calibration of the new Martini 3 small and tiny particle sizes. The models show excellent partitioning behavior and solvent properties. Miscibility trends between different bulk phases are also captured, completing the set of thermodynamic properties considered during the parametrization. We also show how the new bead sizes allow for a good representation of molecular volume, which translates into better structural properties such as stacking distances. We further present design strategies to build Martini 3 models for small molecules of increased complexity.
Establishment of Human Pluripotent Stem Cell‐Derived Skin Organoids Enabled Pathophysiological Model of SARS‐CoV‐2 Infection
Authors: Ma Jie , liu Jia , Gao Dunqin , Li Xiao , Zhang Qiyu , Lv Luye , Wang Yujie , Li Jun , Zhu Yunping , Wu Zhihong , Hu Hengrui , Li Yufeng , Ma Longda , Liu Qian , Hu Zhihong , Zhang Shuyang , Zhou Yiwu , Wang Manli , Leng Ling
Published: December 2021

Coronavirus disease 2019 (COVID‐19) patients with impact on skin and hair loss are reported. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is detected in the skin of some patients; however, the detailed pathological features of skin tissues from patients infected with SARS‐CoV‐2 at a molecular level are limited. Especially, the ability of SARS‐CoV‐2 to infect skin cells and impact their function is not well understood. A proteome map of COVID‐19 skin is established here and the susceptibility of human‐induced pluripotent stem cell (hiPSC)‐derived skin organoids with hair follicles and nervous system is investigated, to SARS‐CoV‐2 infection. It is shown that KRT17+ hair follicles can be infected by SARS‐CoV‐2 and are associated with the impaired development of hair follicles and epidermis. Different types of nervous system cells are also found to be infected, which can lead to neuron death. Findings from the present work provide evidence for the association between COVID‐19 and hair loss. hiPSC‐derived skin organoids are also presented as an experimental model which can be used to investigate the susceptibility of skin cells to SARS‐CoV‐2 infection and can help identify various pathological mechanisms and drug screening strategies.
Organic Log‐Domain Integrator Synapse
Authors: Hosseini Mohammad Javad Mirshojaeian , Donati Elisa , Indiveri Giacomo , Nawrocki Robert A.
Published: December 2021

Synapses play a critical role in memory, learning, and cognition. Their main functions include converting presynaptic voltage spikes to postsynaptic currents, as well as scaling the input signal. Several brain‐inspired architectures have been proposed to emulate the behavior of biological synapses. While these are useful to explore the properties of nervous systems, the challenge of making biocompatible and flexible circuits with biologically plausible time constants and tunable gain remains. Here, a physically flexible organic log‐domain integrator synaptic circuit is shown to address this challenge. In particular, the circuit is fabricated using organic‐based materials that are electrically active, offer flexibility and biocompatibility, as well as time constants (critical in learning neural codes and encoding spatiotemporal patterns) that are biologically plausible. Using a 10 nF synaptic capacitor, the time constant reached 126 and 221 ms before and during bending, respectively. The flexible synaptic circuit is characterized before and during bending, followed with studies on the effects of weighting voltage, synaptic capacitance, and disparity in presynaptic signals on the time constant.
Tuning the Structure, Magnetic, and High Frequency Properties of Sc‐Doped Sr0.5Ba0.5ScxFe12‐xO19/NiFe2O4 Hard/Soft Nanocomposites
Authors: Almessiere Munirah A. , Slimani Yassine , Algarou Norah A. , Vakhitov Maksim G. , Klygach Denis S. , Baykal Abdulhadi , Zubar Tatyana I. , Trukhanov Sergei V. , Trukhanov Alex V. , Attia Hussein , Sertkol Murat , Auwal İsmail A.
Published: December 2021

The Sr0.5Ba0.5ScxFe12–xO19(SrBaSc)/NiFe2O4(NiFe) hard–soft nanocomposites (NCs) are synthesized by in situ sol–gel route. Impact of Sc3+ doping on their structure, morphology, and magnetic properties are examined. X‐ray diﬀraction confirms the coexistence of SrBaSc and NiFe phases without any impurity. Morphology of NCs reveals a cluster of hexagonal plate decorated by spherical grains. Magnetic characteristics of the NCs are examined by using a vibration sample magnetometer at room temperature and 10 K. The x = 0.000 sample shows some kinks in their M–H loops and the occurrence of two peaks in dM/dH(H). All the NCs with Sc3+ exhibit smooth shapes of M–H curves with single peak, revealing the complete and perfect exchange coupling behavior. The diverse magnetic parameters at both temperatures are determined. The values of saturation and remanent magnetizations are decreasing with the Sc content increase. The intensive electromagnetic absorption is observed in all the samples. Reﬂection loss (RL) of more than ‐18 dB is observed above 3 GHz. Strong coupling between Sc concentration and amplitude–frequency characteristics of the RL can be used for developing of the functional media for high‐frequency devices and will open broad perspectives for practical application in radar‐absorbing technology and electromagnetic compatibility.
In‐Situ Loading Bridgman Growth of Mg3Bi1.49Sb0.5Te0.01 Bulk Crystals for Thermoelectric Applications
Authors: Wang Qi‐Qi , Li Fan , Xia Sheng‐Qing , Liu Jian , Liu Xiao‐Cun , Chen Ling , Zhang Cheng‐Qian
Published: December 2021

The single crystal growth of Mg3Bi2‐based thermoelectric materials is of great significance for their applications near room temperature. So far, it is still a big challenge to grow such bulk single crystals and attempts are primarily focused on the metal flux methods. For the first time, bulk single crystals of n‐type Mg3Bi1.49Sb0.5Te0.01 are directly grown by applying an In‐situ Loading Bridgman method. The as‐grown single crystal features an excellent carrier mobility of 220 cm2 V−1 s−1, which is among the best compared to other Mg3Bi2‐based bulk materials. Besides, this method is successfully developed to fast grow uniform polycrystalline materials with high thermoelectric and mechanic performance. As demonstrated by the single‐leg device, a large temperature difference of 10.5 K is achieved at the supplied electric current of 0.6 A, much superior to other room temperature state‐of‐the‐art thermoelectric materials. With the single crystalline and polycrystalline materials prepared reliably and conveniently, in‐depth investigations on the Mg3Bi2 thermoelectric system can be greatly benefited, which should as well significantly facilitate their practical applications at room temperature.
Bio‐Inspired Computational Design of Vascularized Electrodes for High‐Performance Fast‐Charging Batteries Optimized by Deep Learning
Authors: Sui Chenxi , Li Yao‐Yu , Li Xiuqiang , Higueros Genesis , Wang Keyu , Xie Wanrong , Hsu Po‐Chun
Published: December 2021

Slow ionic transport and high voltage drop (IR drop) of homogeneous porous electrodes are the critical causes of severe performance degradation of lithium‐ion batteries at high charging rates. Herein, it is numerically demonstrated that a bio‐inspired vascularized porous electrode can simultaneously solve these two problems by introducing low tortuous channels and graded porosity, which can be verified by porous electrode theory. To optimize the vasculature structural parameters, artificial neural networks are employed to accelerate the computation of possible structures with high accuracy. Furthermore, an inverse‐design searching library is compiled to find the optimal vascular structures under different industrial fabrication and design criteria. The prototype delivers a customizable package containing optimal geometric parameters and their uncertainty and sensitivity analysis. Finally, the full‐vascularized cell shows a 66% improvement in charging capacity compared to the traditional homogeneous cell under 3.2 C current density in a numerical simulation. This computational research provides an innovative methodology to solve the fast‐charging problem in batteries and broaden the applicability of deep learning algorithms to different scientific or engineering areas.
Dementia care in China: Challenges and recommendations
Authors: Zhao Wenhong
Published: December 2021

Background

In China, approximately 84.9% of people with dementia are cared for by family caregivers. Health professionals working in the departments where people with dementia are cared for in public tertiary hospitals are the primary sources to offer a formal diagnosis and treatment to people with dementia in China. The aim of this study was to explore family caregivers’ expectations on dementia care, and the dementia knowledge and attitudes of health professionals in China.

Method

Mixed method was used to collect data from April to December 2019. Surveys were used to evaluate health professionals’ (n=603) dementia knowledge and attitudes in eleven public tertiary hospitals in Hebei Province in China. Semi‐structured interviews were conducted in three public tertiary hospitals where family caregivers of people with dementia (n=21) were recruited.

Result

The health professionals demonstrated limited knowledge of dementia and a low level of positive attitude. They expressed that it was challenging to communicate with people with dementia and to cope with their symptoms. Family caregivers reported that they received limited support from the community, hospital, and society and they held little hope of receiving such support. Most of the caregivers expected more financial support from the government, and more training in dementia care from health professionals. They also expressed their desire to have a professional caregiver in the nursing homes to provide optimal dementia care for their relatives.

Conclusion

Health services in China are inadequately prepared to deal with the challenges of dementia care. More emphasis is needed on specialized education and training for caregivers and health professionals to improve their knowledge and to modify their attitudes. Family caregivers expected more support from the health system to enable improved care for people with dementia. An integrated health system for dementia care is needed in China.
Computational identification of inhibitors of MSUT‐2 using quantum machine learning and molecular docking for the treatment of Alzheimer's disease
Authors: Ganesh Rithvik
Published: December 2021

Background

Alzheimer's Disease is in a class of related neurodegenerative diseases known as tauopathies, where tau hyperphosphorylation leads to progressive neurological decline. MSUT‐2 has emerged as a viable target for the treatment of tauopathies like Alzheimer's, as the protein's interactions with the tau protein could be central to the accumulation and aggregation of tau. Quantum Computing and Machine Learning are two developing fields that have the capability to completely revolutionize the field of pharmacology. Developed architectures like Quantum Support Vector Machines can be scaled up readily as technology improves, further enhancing this breakthrough field’s implications on pharmacology.

Method

In the first phase of research, OpenEye's FILTER software was employed, which eliminated a set of starting compounds from ChemBridge's EXPRESS‐PICK Screening Library (over 500,000 compounds) that were predicted to be highly toxic and have low bioavailability. Next, a simple pharmacophore screen was performed using a set of known partial actives and inactives on OpenEye's ROCS tool. A modified Quantum Support Vector Machine algorithm was then run through IBM Qiskit. The model was trained using dozens of known chemical features of FDA‐approved chemical actives and inactives. Compounds were featurized using data from SwissADME. Following preprocessing and training, the model was executed to predict known actives from the remaining set of test compounds. Finally, compounds were subject to a precise molecular docking trial with MSUT‐2 (using OpenEye’s FRED tool and AUTODOCK Vina), where binding interaction strength was directly evaluated.

Result

This computational screening methodology resulted in numerous predicted inhibitors of MSUT‐2. To validate the methodology of this screening workflow, numerous known FDA‐approved drugs and actives for other diseases were successfully identified using the exact screening methodology utilized in this experiment through retrospective analysis.

Conclusion

In conclusion, a promising computational screening methodology partially validated with translational data using advancements in Quantum Machine Learning has been identified. This exact workflow is novel and promising, and can easily be scaled up for comprehensive screening for a myriad of targets. 5 inhibitors for a promising yet underexplored target for Alzheimer’s disease, MSUT‐2, have also been identified in this study.
HOMESIDE—A home‐based family caregiver‐delivered music and reading intervention for people living with dementia: A randomised controlled trial
Authors: Baker Felicity , Odell‐Miller Helen , Wosch Thomas , Stensaeth Karette , Bukowska Anna , Clark Imogen
Published: December 2021

Background

Pharmacological interventions to address behavioural and psychological symptoms of dementia (BPSD) can have undesirable side effects, therefore non‐pharmacological approaches to managing symptoms may be preferable. Past studies show that music therapy can reduce BPSD, and other studies have explored how formal caregivers use music in their caring roles. However, no studies have examined the effects on BPSD of music interventions delivered by informal caregivers (CGs) in the home setting. Our project addresses the need for improved informal care by training cohabiting family CGs to implement music interventions that target BPSD, and the quality of life (QoL) and well‐being of people with dementia and CGs.

Methods

An international three‐arm parallel‐group randomised controlled trial has so far randomised 130 of the target 495 dyads from Australia, Germany, UK, Poland and Norway. Dyads are randomised equally to standard care (SC), a home‐based music programme plus SC, or a home‐based reading programme plus SC for 12 weeks. The primary outcome is BPSD of people with dementia (measured using the Neuropsychiatric Inventory‐Questionnaire). Secondary outcomes examine relationship quality between CG and people with dementia, depression, resilience, competence, QoL for CG and QoL for people with dementia. Outcomes are collected at baseline, at the end of the 12‐week intervention and at 6 months post randomisation. Resource Utilisation in Dementia captures economic data across the life of the intervention and at 6‐month follow‐up. Our presentation will briefly outline the study protocol and describe the caregiver training protocol and interventions in detail with video footage illustrating how the intervention looks in practice.
Discovery of screened potential inhibitors for Alzheimer disease responsible enzymes: Insights from atomistic simulations
Authors: Kandasamy Saravanan
Published: December 2021

Background

One of the cruelest neurogenerative disorder is Alzheimer disease (AD) which majorly affects old aged humans. It initially affects a person’s ability to carry out daily functions and leads to death. Basically, many diverse factors are leading to neuronal cell death such as low level of acetylcholine, deposition of amyloid beta, aggregation of tau proteins, oxidative stress, neuro‐inflammation, excitotoxicity, genetic and heredity factors. Some of the recent reports also outline about AD and it was characterized by different hypothesis and are named as cholinergic hypothesis, amyloid hypothesis, tau hypothesis and others (oxidative stress and genetic). Therefore, the present study focused to identify a potential inhibitor to control the level of Alzheimer disease.

Method

We have selected two different databases (ZINC15 and DUNDEE) and four different enzymes (Acetylcholinesterase, Butyrylcholinesterase, β‐Secretase and Glycogen synthase kinase 3 beta) for the study and carried out the high throughput virtual screening (HTVS), molecular docking, molecular dynamics simulation and binding free energy calculation to understand the active site effects and its stability.

Result

In the AChE and BChE, the screened molecules are showing good binding with strong interactions; notably, π‐cationic interactions were observed between amine group of ligand and tyrosine, tryptophan residues of AChE. Whereas in the BChE, active site residue Glu197 is highly stable. The catalytic dyad residue Asp93 of BACE1 maintains their hydrogen bond and Asp133 of GSK3β also sustain the strong interactions during the MD simulation. Apart from this, the statistical parameters (RMSD, RMSF and Rg) of these complexes are acceptable.

Conclusion

In‐silico based analyses demonstrate that all the selected molecules are forming strong hydrogen bonding with catalytic residues and these interactions are highly stable during the atomistic simulation with high affinity. This comparative study allows to understand binding affinity, stability of intermolecular interactions and molecular flexibility of the molecules in the active site of AChE/BChE enzymes. Computational understanding of unproven molecules may lead towards the developing against AD.
Clinical use of deep speech parameters derived from the semantic verbal fluency task
Authors: ter Huurne Daphne BG , Ramakers Inez HGB , Linz Nicklas , König Alexandra , Langel Kai , Lindsay Hali , Verhey Frans RJ , de Vugt Marjolein
Published: December 2021

Background

Previous research showed that semantic memory is a good indicator for cognitive decline in early phases of Alzheimer’s disease. Automatically derived deep speech parameters from the semantic verbal fluency (SVF) can potentially have an additional value to differentiate SCI, MCI and dementia, compared to the total fluency score. However, the added diagnostic value of (specific) deep speech parameters to the commonly clinically used SVF raw score remains unknown. In the Deepspa project, we investigated the (additional) value of automatically derived speech parameters in clinical practice. We also investigated the relation between automatically derived speech parameters of the SVF and other cognitive tasks, as well as disease severity and functioning in daily living.

Method

In the DeepSPA project, 140 participants were recruited from the memory clinic of the MUMC+ (SCI, MCI, ADD). All subjects underwent a cognitive assessment including the SVF. The SVF (animals, 60 seconds) was administered by use of the Delta application (ki elements). Disease severity and functioning in daily life were administered by the Clinical Dementia Rating Scale (CDR) and Disability Assessment for Dementia (DAD) respectively. The agreement between the automatic and clinical raw score of the SVF was assessed by the interclass correlation coefficient. The relation between the deep speech parameters, such as mean word frequency, temporal and semantic clusters, transition time between words etc., and syndrome diagnosis, DAD and CDR were investigated using stepwise regression analyses, corrected for age, education level and gender.

Result

Preliminary results showed that deep speech parameters have an additional value in the classification of clinical diagnosis, and disease severity. More specifically, mean word frequency and the mean time between temporal clusters had an added value. The reliability between word count by the application and the clinician was good (ICC=.882, 95% CI = .820‐.923). Results about the relation between deep speech parameters and other cognitive performances will be available at the conference.

Conclusion

First results suggest that deep speech parameters have an additional value in the early diagnostics of cognitive impairments. More information about the value of these non‐invasive automatically derived deep speech parameters could improve diagnostic accuracy in clinical practice.
An update and baseline data from the phase 2/3 GAIN trial of COR388 (atuzaginstat), a novel bacterial virulence factor inhibitor for the treatment of Alzheimer’s disease
Authors: Detke Mike
Published: December 2021

Background

The novel mechanism of action of atuzaginstat is based on the discovery of gingipains, toxic protease virulence factors from the bacterial pathogen Porphyromonas gingivalis (Pg), in >90% of Alzheimer’s disease (AD) brains. Gingipain levels correlated with AD diagnosis and tau and ubiquitin pathology, and oral infection of mice with Pg results in classic AD pathology that can be blocked by atuzaginstat, an irreversible lysine‐gingipain inhibitor. Pg is best known for its role in periodontal disease. Atuzaginstat was well tolerated in phase 1, including trends of efficacy on clinical scales, and significant improvement on a computerized speech assessment and two relevant biomarkers.

Methods

The Phase 2/3 GAIN trial, designed to be potentially pivotal, completed enrollment in November 2020. 642 subjects (aged 55‐80; mild‐moderate AD with MMSE 12‐24) were randomized to one of two doses of atuzaginstat (40mg or 80mg BID) or placebo. The co‐primary endpoints are mean change in ADAS‐Cog 11 and ADCS‐ADL from baseline to 48 weeks. Additional endpoints include change in CDR‐SB, MMSE, NPI, Winterlight Speech Assessment, CSF and oral biomarkers, MRI and other measures.

Results

Baseline data show that the 642 randomized subjects are: 56.9% female, 64.3% ApoE4 positive, 49.5% mild (MMSE = 19‐24) and 50.5% moderate (12‐18). 73.2% of subjects received symptomatic AD co‐medications. New baseline biomarker data from the full set of subjects in the study will be shared, including anti‐Pg IgG, amyloid‐β peptide ratio 42/40, and phospho tau. 233 GAIN trial patients are also participating in a dental sub‐study, and while not selected for periodontal disease, approximately 90% have moderate ‐ severe periodontitis.

Conclusions

Enrollment of the GAIN trial was completed in November 2020, and top‐line efficacy data are expected December Q4 2021. An interim analysis in December 2020 indicated that the study should continue as planned without sample size adjustment. Subjects enrolled exhibit baseline characteristics consistent with AD and with Pg infection, indicating an appropriate population to test the efficacy and safety of atuzaginstat in mild‐moderate AD. The high correlations of AD, periodontal disease, and Pg infections observed in GAIN replicates findings by others and supports a causal role of Pg in AD.
Technology‐driven dyadic interaction in caregiving
Authors: Hoel Viktoria , Ambugo Eliva Atieno , Steinert Lars , Schultz Tanja , Wolf‐Ostermann Karin
Published: December 2021

Background

Due to the ongoing pandemic and the resulting community lockdowns, people with dementia and their family might be at risk of social deprivation and increased relationship strains. Technological means have the potential to engage participants in meaningful positive interactions. The tablet‐based activation system I‐CARE offers social activities specifically designed for people with dementia and their caregivers, by offering user‐specific contents adapted to their needs and sensitivities. Little is known about the impact of Covid‐19 on social health for this population. The ongoing study, presented as a part of the Marie‐Curie Innovative‐Training‐Network action, H2020‐MSCA‐ITN, grant agreement 813196, assesses how COVID‐19 has impacted community‐dwelling dementia caregiving dyads. Contextual factors of technology use and motivations for inviting technology into social interactions is explored.

Method

As a part an ongoing pre‐post mixed‐methods feasibility study, baseline assessments through semi‐structured interviews were conducted and subjected to inductive thematic statement analysis by two independent researchers.

Result

Participants differed in how COVID‐19 restrictions impacted their lives and how they coped with dementia, revealing different motivations for inviting technology into their lives. Dyads who were socially active pre‐COVID‐19, and who managed use technology to maintain social participation during COVID‐19, reported to have been less negatively impacted by COVID‐19 restrictions. Four subthemes within “Social technology during COVID‐19” were identified.

Conclusion

During and beyond this pandemic, social technology is a valuable tool to promote social participation in this population. Successful uptake of technology is dependent on customizing to individuals’ needs and conditions.
Correspondence of CSF biomarkers measured by Lumipulse assays with amyloid PET
Authors: Volluz Katherine E. , Schindler Suzanne E. , Henson Rachel L. , Xiong Chengjie , Gordon Brian A. , Benzinger Tammie L.S. , Holtzman David M. , Morris John C. , Fagan Anne M.
Published: December 2021

Background

Traditional plate‐based assays for cerebrospinal fluid (CSF) biomarkers have been limited by relatively high assay variance that reduces the accuracy of individual measurements. Next generation automated assay platforms for CSF biomarkers reduce the variability of measurements, including across sample runs. In the current study, we utilized the Lumipulse G1200 (Fujirebio; Malvern, PA), a fully‐automated assay platform to compare CSF biomarkers to brain amyloid burden as determined by positron emission tomography (PET) imaging.

Method

Participants (n=758) were enrolled in studies of memory and aging at the Knight ADRC in St. Louis, Missouri. Concentrations of CSF amyloid‐beta 40 (Aβ40), amyloid‐beta 42 (Aβ42), total tau (tTau) and phosphorylated tau‐181 (pTau) were measured using the Lumipulse G1200 automated assay system. Brain amyloid burden was measured via amyloid PET imaging using Florbetapir or Pittsburgh compound B (PIB). The correspondence of CSF biomarkers with amyloid PET status based on established cut‐offs for each radiotracer was evaluated.

Result

For pooled CSF controls representing a range of three values (low, medium, high), coefficients for inter‐day variability ranged from 2‐4%. CSF collected within two years of an amyloid PET scan was evaluated from 521 amyloid PET‐negative and 237 amyloid PET‐positive individuals. Correspondence with amyloid PET by receiver operating characteristic (ROC) area under the curve (AUC) was highest for ratios including Aβ42: pTau/Aβ42 (0.97, 95% confidence intervals 0.96‐0.99), Aβ42/Aβ40 (0.97, 0.95‐0.98), and tTau/Aβ42 (0.96, 0.94‐0.97). A CSF pTau/Aβ42 value of >0.0649 had the highest combined positive and negative percent agreement (PPA of 0.91, 0.86‐0.94; NPA of 0.96, 0.93‐0.97) with amyloid PET status. The CSF value for Aβ42/Aβ40 with highest combined PPA and NPA was slightly more sensitive but less specific: <0.0673 had a PPA of 0.97 (0.94‐0.99) and NPA of 0.91 (0.88‐0.93) with amyloid PET status.

Conclusion

Measurement of CSF biomarkers with the Lumipulse G1200 automated assay system was highly precise, with low variability over multiple runs. Values for pTau/Aβ42, Aβ42/Aβ40, and tTau/Aβ42 were highly concordant with amyloid PET status.
Survey in people with dementia and their care partners on post‐diagnostic care in memory clinics: Data from the COGNISANCE study
Authors: Hevink Maud , Verhey Frans R.J. , Brodaty Henry , Low Lee‐Fay , Vedel Isabelle , Rymaszewska Joanna , Rait Greta , Robinson Louise ,   the COGNISANCE study group
Published: December 2021

Background

Recent literature calls for a focus on providing quality post diagnostic dementia care (Wong & Knapp, 2020). There is dissatisfaction among people with dementia (PwD) and care partners (CP) with post diagnostic dementia support (Hagan, 2020). To improve experiences of post diagnostic support for PwD and CP, it is vital to understand what factors influence their experience of post diagnostic support. Differences between PwD and CP could be used to tailor support to their respective needs and wishes. The aim of the present study is twofold. First, to determine which factors predict the satisfaction with post‐diagnostic support for PwD and CP. Second, to compare factors of PwD and CP that shape experiences of post diagnostic support.

Method

As part of the COGNISANCE project, a survey was developed and distributed among PwD and CP in five countries: Australia, Canada, the Netherlands, Poland, and the United Kingdom. The survey consisted of mostly closed questions on demographics, experiences of the diagnostic process, and post diagnostic support.

Result

The average age of the PWD respondents (N=91) was 74.3 (+‐ 10.0) and 60.1 (+‐ 14.4) that of the CP respondents (N=209). The majority of the PWD (57.1%) and CP (71.3%) were female. Support after a diagnosis was deemed helpful by 57.4% of the PWD and 62% of the CP. There is a significant association between whether PWD and CP were satisfied with support and their satisfaction with the diagnostic process, satisfaction with information on dementia and information on strategies to live well with dementia. For PWD, satisfaction with support is associated with the waiting time for a first appointment in the diagnostic process, the satisfaction with the waiting time, confidence in asking for help, confidence in handling future challenges and living positively with dementia.

For CP, the satisfaction with support was associated with the presence of a care plan, their satisfaction with information on prognosis and information on services.

Conclusion

A significant minority of PwD and CP is not satisfied with the support following a diagnosis. Results suggest that information aspects and experiences in the diagnostic process impact on the satisfaction with dementia support.
Improved comparability between measurements of mean cortical amyloid plaque burden derived from different PET tracers using multiple regions‐of‐interest and machine learning
Authors: Chen Kewei , Ghisays Valentina , Luo Ji , Chen Yinghua , Lee Wendy , Benzinger Tammie L.S. , Wu Teresa , Reiman Eric M. , Su Yi
Published: December 2021

Background

The conversion of standard uptake value ratios (SUVRs) to Centiloid units using previously described methods has partially but not completely improved the ability to compare measurements of mean cortical amyloid plaque burden, classify positive versus negative amyloid PET scans, assess changes over time, and evaluate amyloid‐modifying treatment effects using different radiotracers. Here, we demonstrate improved harmonization between PiB and florbetapir (FBP) PET measurements of mean cortical SUVRs (mcSUVRs) using multiple regions‐of‐interest (ROIs) and machine learning algorithms.

Methods

PiB and FBP PET image pairs from 91 subjects in the Open Access Series of Imaging Studies (https://www.oasis‐brains.org/) were used as the training set to optimize the algorithms to generate each subject’s pseudo‐PiB mcSUVR measurements from his or her FBP multi‐ROI SUVRs . PiB and FBP image pairs from 46 subjects in the Avid‐related Centiloid Project (www.gaain.org/centiloid‐project) were then used as the test set to compare Pearson’s correlation coefficients (r) between the pseudo and actual PiB mcSUVR measurements using our approach to that used in the Centiloid method. SUVRs with cerebellar reference were extracted from multi‐ROIs using FreeSurfer with partial volume correction. Pseudo mcSUVRs were generated using ensemble regression, partial least square regression (PLSR) and artificial neural network (ANN) separately, and their correlations with the actual PiB mcSUVR were compared to the PiB‐FBP correlation on Centiloid in both training and test sets.

Results

In the training set, the Centiloid based PiB‐FBP correlation was r=0.904. An ANN with 7/6 neurons in the 1st/2nd hidden layers improved it to 0.987 (p≤8.3e‐12) and PLSR to 0.973 (p≤3.8e‐5). In the independent test set, ANN improved r to 0.981 from 0.927 (p≤6.6e‐4) and PLSR to 0.964 (p=0.011). Ensemble regression did not improve r.

Conclusion

The ANN and PLSR algorithms mapping multi‐ROI FBP SUVRs to PiB mcSUVR appear to increase the comparability between measurements of mean cortical amyloid plaque burden using different PET tracers. Additional studies are needed to demonstrate the generalizability to other amyloid PET tracers, clarify its comparability in distinguishing between positive and negative amyloid PET scans, demonstrate its value in longitudinal studies and clinical trials, and extend our approaches to different tau PET ligands.
Age‐stratified, sex‐specific differences in cognitive performance based on risk of obstructive sleep apnea and systemic inflammation: A cross‐sectional analysis of the Canadian Longitudinal Study of Aging
Authors: Legault Julie , Thompson Cynthia , Moullec Gregory , Martineau‐Dussault Marie‐Ève , Baltzan Marc , Cross Nathan , Dang‐Vu Thien Thanh , Gervais Nicole J , Einstein Gillian , Hanly Patrick , Ayas Najib , Lorrain Dominique , Kaminska Marta , Gagnon Jean‐François , Lim Andrew , Carrier Julie , Gosselin Nadia
Published: December 2021

Background

Growing evidence supports associations between cognitive impairment and obstructive sleep apnea (OSA). Our study aimed at determining the age and sex‐specific, independent relationship between risk of having OSA and cognitive performance, and the influence of systemic inflammation on this relationship.

Method

Our sample included 25,712 participants from the Canadian Longitudinal Study of Aging (CLSA) comprehensive cohort aged 45 to 85 years (M = 63 years; 51% women; 78% with post‐secondary degree). Exclusion criteria included Alzheimer’s and Parkinson’s disease and history of stroke and of traumatic brain injury. Participants were classified as high‐ or low‐risk of having OSA based on the STOP questionnaire (high‐risk = ≥ 2/4), considering signs and symptoms associated with OSA including snoring (S), tiredness (T), observation of apneas (O), and high blood pressure (P). Neuropsychological tests assessed memory, executive functioning and psychomotor speed. Levels of high‐sensitivity C‐reactive protein (hs‐CRP) were obtained through blood samples. We conducted sex‐ and age‐specific (45‐59; 60‐69; ≥70) General Linear Models between cognitive scores and risk of OSA, and moderation and mediation analyses with levels of hs‐CRP. Analyses were adjusted for socio‐demographic, lifestyle and medical comorbidities.

Result

In the fully adjusted model, 45‐59 years old women at high‐risk of OSA presented poorer short‐term memory and learning (Rey Auditory Verbal Learning Test, immediate recall, p=0.040), and executive functioning (Animal Fluency test, p=0.011; Mental Alternation test, p=0.006; Stroop Test, inhibition condition, p=0.047; low‐interference index, p=0.027 and high‐interference index, p=0.022) compared to those at low‐risk of OSA. These associations were not found in women aged ≥60 and in men of all age groups. The association between OSA risk and cognition was not moderated by education nor consistently moderated or mediated by the level of hs‐CRP.

Conclusion

These findings suggest that OSA might represent a modifiable risk factor of early cognitive impairment in women aged 45‐59. We suggest clinicians systematically screen for cognitive impairment when patients of this group present suspected or diagnosed OSA. Furthermore, it is important to track changes in cognitive profile of women aged 45‐59 in the CLSA cohort to identify those at risk of long‐term cognitive decline.
The perception of professionals in the socio‐health field about the support services provided for families with a member with neurodegenerative disease
Authors: Montes‐López Estrella , del Álamo‐Gómez Nuria , Yurrebaso‐Macho Amaia , Valverde Eva María Picado ,   NEUROQUALYFAM group
Published: December 2021

Background

In the Spanish case, the social organization of care is characterized by being family oriented. This means that the involvement of the family in the care of its members is high in relation to the participation of other social actors, such as the State, the market, or the community. Neurodegenerative diseases (ND) significantly affect the quality of life of the person, but also that of their family, precisely because of their high involvement in care. Families require support services to increase their well‐being, and several studies have shown the impact that the absence of support services has on the Family Quality of Life (FQoL). Considering this, the main objective of this study is to find out the perception of professionals working in the socio‐health field about the adequacy and sufficiency of the services available to people with ND and their families in the Spain‐Portugal cross‐border area.

Method

This research has been developed through qualitative methodology. Three focus groups were held. They involved: 1) public social services personnel; 2) public health services staff; 3) workers in the services offered by private initiatives. All of them carried out their work in the cross‐border area studied. With the support of the Atlas.ti software and following a deductive coding model, the data obtained were systematically coded and interpreted.

Results

Initial research results suggest that professionals in the socio‐health field agree on their perceptions of the adequacy and sufficiency of support services provided for families with a member with ND. They consider that:

1) most support services are aimed solely at the needs of the person with a ND and therefore contribute little to improving the FQoL;

2) support services considered very adequate for the improvement of the FQoL are very insufficient; 3) the characteristics of the environment (small population, geographical dispersion, etc.) significantly limit support services in rural areas

Conclusion

The support services provided for families with a member with ND are scarce and inadequate, and therefore contribute little to improving the FQoL. There is a need to improve access and adapt support services to the needs of families.