bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cortical microstructural MRI for detection of early target engagement in AD drug trials: post‐hoc analysis of exploratory outcomes from a Phase 1b safety study for XPro1595 in AD
Authors: Pope Parris , Ridgway Gerard R , Barnum CJ , Torso Mario , Chance Steven A , Tesi RJ 
Published: December 2023

AbstractBackgroundEvidence in support of the amyloid cascade hypothesis for Alzheimer’s disease (AD) suggests that pathological amyloid‐beta (Aβ) is initially associated with synaptic hyperactivity and accumulates in an activity dependent fashion. These findings are corroborated by longitudinal data from cohort studies with Aβ‐PET imaging, wherein Aβ accumulates first in gray matter (GM) cortices associated with the default‐mode network (DMN) before spreading in a semi‐hierarchical pattern to different neocortical regions as the disease progresses (Mattsson et al. 2019). Mapping brain regions most frequently affected by Aβ pathology at different stages of disease may provide a framework for investigation of new drug entities targeting other components of Aβ toxicity using less invasive imaging modalities. The hypothesis here is that indicators of disease specific, tissue‐level treatment effects should be first detectable in brain regions most frequently affected by active pathology.MethodXPro1595 is a selective, brain penetrant neutralizer of soluble TNF with potent anti‐neuroinflammatory effects recently assessed for safety and pharmacological activity in a small, open‐label phase‐1b dose finding study (NCT03943264) in patients with AD. Clinical trial results for patients (n = 9) with analyzable dMRIs who completed 12‐weeks of treatment with XPro1595 [0.3 mg/kg; n = 3) or (1.0 mg/kg; n = 6)] met criteria for post‐hoc analysis. Exploratory outcomes included the novel cortical diffusivity measurement PerpPD+. PerpPD+ represents the diffusion components perpendicular to cortical GM minicolumns, indicates microscopic disruption when increased, and has proven more sensitive than standard volumetrics to changes in indicators of synaptic function, neuroinflammation and neurodegeneration across the AD continuum.ResultMean MMSE scores at baseline were 23.7 (SD = 2.5) and 15.8 (SD = 7.0) in the low‐dose and high‐dose groups, respectively, indicating varying degrees of severity. Week‐12 results showed decreases in bilateral PerPD+ at the whole brain level and in multiple GM cortices documented in the literature with the highest frequency of early (precuneus, isthmus cingulate, posterior cingulate, insula, and lateral and medial orbitofrontal) and late (lingual, pericalcarine, paracentral, precentral, and postcentral) Aβ accumulation (Figures1‐2).ConclusionCortical diffusivity measurements related to minicolumnar microstructure may provide an opportunity for noninvasive detection of early, disease specific, tissue‐level target engagement in clinical trials for investigational new drugs in AD.
Working and episodic memory trajectories over time following bilateral oophorectomy in early midlife women
Authors: Gravelsins Laura , Reuben Rebekah , Brown Alana , Gervais Nicole J , Almey Anne , Duchesne Annie , Karkaby Laurice , Perovic Mateja , Witt Suzanne Tyson , Classon Elisabet , Lykke Nina , Theodorsson Elvar , Lundqvist Elisabeth Åvall , Kjølhede Preben , Engström Maria , Jacobson Michelle , Bernardini Marcus , Foulkes William , Page‐Gould Elizabeth , Hampson Elizabeth , Einstein Gillian 
Published: December 2023

AbstractBackgroundEarly ovarian hormone deprivation due to bilateral salpingo‐oophorectomy (BSO; ovarian and fallopian tube removal) is a risk for late‐life AD, but estradiol replacement therapy (ERT) may be protective (Rocca et al., 2007). Working and episodic memory decrements have been observed without ERT soon after surgery (Sherwin et al., 1988) and on average 5 years post‐BSO in midlife compared to premenopausal controls (Gervais et al., 2020). Unknown is whether memory continues to decrease over time in early midlife, a critical period for understanding cognitive trajectories that presage AD. We investigated memory changes in early midlife over time post‐BSO, and whether those taking ERT had different trajectories than those without.MethodParticipants with BSO taking ERT (BSO+ERT: M
age = 44.5y; n = 71) were compared to those not taking ERT (BSO: M
age = 43.2y; n = 55), recruited from Toronto and Montreal, Canada, and Linköping, Sweden, and completed up to four yearly visits. Episodic memory was evaluated using Logical Memory Task (LM) percent forgetting and Rey Auditory Verbal Learning Test (RAVLT) total learning. Working memory was assessed using Spatial Working Memory Task (SPWM) trial 1 errors, Digit Ordering Task (DOT) errors, and Digit Span Backward Task (DSB) span length. Multilevel models were used to examine whether ERT influenced memory over time post‐BSO and disaggregate within‐ and between‐person effects. Estimated marginal means (Aiken and West, 1991) were calculated to delineate significant interactions.ResultThere were no significant changes over time post‐BSO on LM or RAVLT. The DSB showed significant within‐ and between‐person effects; the BSO group showed decreases in span length over time post‐BSO, while the BSO+ERT group showed increases and had significantly longer span lengths at seven years post‐BSO and beyond (Fig.1A&B). The SPWM Task showed a significant within‐person effect; the BSO group had stable errors over time post‐BSO, while the BSO+ERT group had working memory improvements and made fewer errors (Fig.1C).ConclusionFindings suggest that immediate verbal episodic memory declines we observed previously may stabilize. They also reveal that without ERT, most women have working memory declines post‐BSO. These data support ERT administration post‐BSO for working memory preservation. If ERT is contraindicated, cognitive training or lifestyle interventions may mitigate working memory declines.
SPIN90 Deficiency Ameliorates Amyloid ß Accumulation by Regulating APP Trafficking in AD Model Mice
Authors: Kim Sung Hyun 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD), a common form of dementia, is caused in part by the aggregation and accumulation in the brain of amyloid ß (Aß), a product of the proteolytic cleavage of amyloid precursor protein (APP) in endosomes. Trafficking of APP, such as surface‐intracellular recycling, is an early critical step required for Aβ generation. Less is known, however, about the molecular mechanism regulating APP trafficking. This study investigated the mechanism by which SPIN90, along with Rab11, modulates APP trafficking, Aβ motility and accumulation, and synaptic functionalityMethodThis study utilized live‐imaging technology with molecular, cellular and 5xFAD model mice system.ResultBrain Aβ deposition was lower in the progeny of 5xFAD‐SPIN90KO mice than in 5xFAD‐SPIN90WT mice. Analysis of APP distribution and trafficking showed that the surface fraction of APP was locally distinct in axons and dendrites, with these distributions differing significantly in 5xFAD‐SPIN90WT and 5xFAD‐SPIN90KO mice, and that neural activity‐driven APP trafficking to the surface and intracellular recycling were more actively mobilized in 5xFAD‐SPIN90KO neurons. In addition, SPIN90 was found to be cotrafficked with APP via axons, with ablation of SPIN90 reducing the intracellular accumulation of APP in axons. Finally, synaptic transmission was restored over time in 5xFAD‐SPIN90KO but not in 5xFAD‐SPIN90WT neuronsConclusionThe interaction of SPIN90 and Rab11 is implicated in Aβ production through the regulation of APP trafficking.
Brief Continuous Recognition Task for Early Alzheimer Detection and Tracking
Authors: Ashford John Wesson 
Published: December 2023

AbstractBackgroundAlzheimer’s Disease (AD) affects memory processing in the brain. An important aspect of AD assessment and study is memory testing, which can be done with excellent efficiency using a Continuous Recognition Test (CRT). A CRT was designed for online administration to provide 25 unique, complex, interesting images, which were initially presented for up to 3 seconds, and 25 repeated images, which required a response to indicate recognition (takes about 90 seconds). The images include 5 from each of 5 categories, from a set of 3,000 images, ensuring that a broad spectrum of memory is interrogated. The selected images are culturally neutral, and the instructions are provided in 120 languages, so the test is comparable across most countries, and performance is not affected by racial, cultural, or ethnic variations. The test is engaging and has been taken by many individuals over 100 times and by several individuals over 1,000 times. Two studies have compared this test with the Montreal Cognitive Assessment (MoCA) (in China and Netherlands) and found that this test performed at least as well.MethodData was examined from over a million CRT administrations from 3 sources: at the URL: www.memtrax.com, including over 18,000 unique users recruited by a French company (HAPPYneuron, INC), over 200,000 unique users from free access, and over 90,000 unique users from a free recruitment program (www.brainhealthregistry.org, part of the Alzheimer’s Disease Neuroimaging Initiative). Response time data was available for every image of each CRT, and the 3 populations were evaluated for HITs (correct recognitions), Correct Rejections (CRs, not responding to a new image), and response time to HITs (RT), including average RTs.ResultAnalyses indicated that 97% of individuals, across sites who scored better than chance (65% correct), performed better than 80% correct. Percent HITs and CRs and RTs showed a dichotomy with HITs (recognitions) correlating with RT (an AD dysfunction), while a separate group had fewer correct rejections (response disinhibition) and RT inconsistency, presumably related to fronto‐temporal dementia (clinical observation). Statistical analysis provides precision of impairment estimation.ConclusionA CRT can be used for early AD screening, memory assessment, and progression tracking.
Facial emotional recognition in patients with dementia, part of the ReDLat study
Authors: Moreno Maria Jose , Garcia Deissy Milena , Buitrago Carlos Felipe , Forero Laura Valentina , Rivera Carlos , Reyes Pablo A , Matallana Diana 
Published: December 2023

AbstractBackgroundThe social domain impairments associated with Alzheimer’s disease and frontotemporal lobar degeneration have been linked to basic neurocognitive processes such as visual emotion identification through facial expressions.MethodIn this study, we explore the recognition of seven basic emotions presented in the Mini‐SEA test in a sample of 84 Colombian individuals with dementia (32 with Alzheimer’s Disease and 30 with Frontotemporal Dementia) and compare it with 22 healthy participants from the RedLat study.ResultThe results of the behavioral performance show a lower performance in people with dementia compared to healthy subjects, however, no significant differences are reported between the patient group (AD and FTD).ConclusionThese findings may be associated with the clinical heterogeneity of the evaluated subjects.References:Couto, B., Manes, F., Montañés, P., Matallana, D., Reyes, P., Velasquez, M., … Ibáñez, A. (2013). Structural neuroimaging of social cognition in progressive non‐fluent aphasia and behavioral variant of frontotemporal dementia. Frontiers in Human Neuroscience, 7. https://doi.org/10.3389/fnhum.2013.00467
Hot, P., Klein‐Koerkamp, Y., Borg, C., Richard‐Mornas, A., Zsoldos, I., Paignon Adeline, A., … Baciu, M. (2013). Fear recognition impairment in early‐stage Alzheimer’s disease: When focusing on the eyes region improves performance. Brain and Cognition, 82(1), 25‐34. https://doi.org/10.1016/j.bandc.2013.02.001
¿Frontotemporal dementia or Alzheimer’s disease? Phenotypic variability in a large family with neurodegenerative disorders
Authors: Garcia Deissy Milena , Buitrago Carlos Felipe , Moreno Maria Jose , Forero Laura Valentina , Triviño Cristian , Lopez Greizy , Duran Clemencia , Reyes Pablo A , Gelvez Nancy , Matallana Diana 
Published: December 2023

AbstractBackgroundThe frontal variant of Alzheimer’s disease is characterized by behavioral changes and executive deficits in the early stages. This phenotype is similar in the behavioral variant of frontotemporal dementia, hindering the clinical diagnosis. The aim of this study is to describe the profile of cognitive, behavioral and motor disorders in a family with an autosomal dominant inheritance pattern of early‐onset dementia.MethodFive cases of affected individuals of a Colombian family are presented. We conducted an interdisciplinary clinical evaluation involving different specialties including geriatric, neurology, psychiatry, neuropsychology, and genetics. After each individual evaluation, a consensus was reached among the specialists to define the diagnosis.ResultIn all cases, reported age of onset was before 60 years old. Three out of four cases met criteria for severe dementia and the remaining case presented Mild Cognitive Impairment (MCI). In two cases, the first symptoms reported were memory and planification problems that affected daily life activities. Nevertheless, at the formal evaluation, predominant changes at the executive functions and social cognition were found. In the other two cases, given the severity of the alterations, the evaluation was limited to the analysis of the clinical history, and it is suspected to be cases of linguistic variants of FTD.ConclusionIntrafamilial phenotypic variability was described in this family. This variability in the presentation of the disease phenotype could guide the clinical diagnosis.References:Ossenkoppele, R., Singleton, E. H., Groot, C., Dijkstra, A. A., Eikelboom, W. S., Seeley, W. W., … & Pijnenburg, Y. A. (2022). Research criteria for the behavioral variant of Alzheimer disease: a systematic review and meta‐analysis. JAMA neurology, 79(1), 48‐60.Musa, G., Slachevsky, A., Muñoz‐Neira, C., Méndez‐Orellana, C., Villagra, R., González‐Billault, C., … & Lillo, P. (2020). Alzheimer’s disease or behavioral variant frontotemporal dementia? Review of key points toward an accurate clinical and neuropsychological diagnosis. Journal of Alzheimer’s disease, 73(3), 833‐848.
A Modified Quasi‐Classical Analysis to Capture the Effects of Strong Interaction in Open QED Lattices
Authors: Tiwari Tarush , Shrivastava Kuldeep K , Roy Dibyendu , Singh Rajeev 
Published: December 2023

AbstractThe role of optical nonlinearity in light propagation through two different 1D open QED lattices is investigated, namely a chain of qubits with direct coupling between the nearest neighbors and a chain of connected resonators to each of which a qubit is side‐coupled. Using the more accurate truncated Heisenberg‐Langevin equations method, a reduction of light transmission with increasing intensity in these lattices is shown due to effective photon–photon interactions and related photon blockade mediated by nonlinearity in qubits. In contrast to the direct‐coupled qubits, a revival in the light transmission is found in the side‐coupled qubits at relatively higher intensities due to saturation of qubits by photons. In absence of bulk dissipation, it is found that the standard quasi‐classical analysis fails to capture the reduction in light transmission due to effective photon–photon interaction. A systemic method is devised to modify the quasi‐classical analysis to give much better results.
Effects of cross‐linked networks on dielectric properties of epoxy resins based on molecular dynamics
Authors: Wang Yifang , Du Boxue , Kong Xiaoxiao , Li Xiaolong 
Published: December 2023

AbstractIn this paper, three epoxy resin systems commonly used in power equipment are prepared to obtain cross‐linked networks with structural differences. The relationship between microscopic structures and dielectric properties of epoxy resins is investigated and discussed. Experimental results show that the polarization and conductance losses are inhibited in the anhydride‐cured systems with methyl groups. The molecular dynamics (MD) simulation shows that rigid anhydride structures (such as methyl groups) play a major role in reducing the local segment mobility and increasing the free volume at cross‐linking points. The decrease in local segment mobility has been confirmed by the decrease of mean square displacement (MSD) at the cross‐linking points, which is consistent with the change of measured polarization and conductance loss. In the glassy state, the dielectric properties of different anhydride‐cured systems can be reflected by local MSD at the cross‐linking points. At high temperatures near the glass transition temperature, both the free volume and network mobility increase significantly, which reflects the increased dielectric relaxation strength and conductance loss. The understanding of the structure–property relationships could provide a theoretical foundation for epoxy modification in a controlled manner for power equipment applications.
Higher 1‐year mortality on rest days in patients with acute coronary syndromes and decompensated heart failure—A SPUM‐ACS sub‐study
Authors: Matter Michael A. , Candreva Alessandro , Stähli Barbara E. , Heg Dik , Klingenberg Roland , Räber Lorenz , Windecker Stephan , Rodondi Nicolas , Nanchen David , Mach François , Gencer Baris , Ruschitzka Frank , Matter Christian M. , Templin Christian 
Published: December 2023

AbstractBackgroundAcute coronary syndromes (ACS) occurring on rest days have been associated with higher mortality, but the current literature remains inconsistent in this regard. This study included ACS patients presenting with acute decompensated heart failure (ADHF) investigating the relationship between time of coronary catheterization and outcomes.MethodsAnalyses were performed from the prospective, multicentric Special Program University Medicine Acute Coronary Syndromes and Inflammation (SPUM‐ACS) Cohort. Patients were divided into two groups according to time of coronary catheterization on either workdays (Monday, 00:00 to Friday, 23:59) or rest days (Saturday, 00:00 to Sunday, 23:59 and public holidays). ADHF was defined by Killip Class III or IV upon presentation. Patients were followed over 1 year.ResultsOut of 4787 ACS patients enrolled in the SPUM‐ACS Cohort, 207 (4.3%) presented with ADHF. 52 (25.1%) and 155 (74.9%) patients underwent coronary angiography on rest days or workdays, respectively. Baseline characteristics were similar among these groups. ACS patients with ADHF showed increased 1‐year mortality on rest days (34.6% vs. 17.4%, p‐value = 0.009). After correction for baseline characteristics, including the GRACE 2.0 Score, rest day presentation remained a significant predictor for 1‐year mortality (adjusted hazard ratio = 2.42 [95% confidence interval: 1.14–5.17], p‐value = 0.022).ConclusionsOne‐year all‐cause mortality was high in ACS patients with ADHF and doubled for patients admitted on rest days. The present data support the association of a rest day effect and long‐term patient survival and indicate a need for further investigations.
Rise up: Career empowerment, adaptability and resilience during a pandemic
Authors: Grabarski Mirit K. , Mouratidou Maria 
Published: December 2023

AbstractThe present article examines employee resilience during the COVID‐19 pandemic, which created a major career disruption and a psychological strain for many individuals worldwide. Resilience is an essential psychological resource for coping with setbacks and maintaining mental health. Using a time‐lagged survey design, we test a theoretical model that links career empowerment, a motivational cognitive construct, with resilience, mediated by career adaptability. Our findings support these hypotheses. In addition, we investigate the moderating role of neuroticism and authentic leadership in the relationship between the career empowerment and career adaptability. Findings show that while authentic leadership moderates this relationship, the hypothesis regarding neuroticism was not supported. Our research provides insights regarding resilience during crisis, which has both theoretical and practical implications.
Preparation and Characterization of Nanocomposite Perovskite Cathode Materials La0.3Sr0.7Fe0.4Ti0.6O3‐δ (LSFT) for Low‐Temperature SOFCs with Incorporation of Graphene Oxide (GO)
Authors: Ahmad Khalil , Abbas Ghazanfar , Ahmad M. Ashfaq , kazim Zafarullah , Munir Tariq 
Published: December 2023

AbstractThe porous and mixed ionic electronic cathode conductor plays a vital role in the efficient working of low‐temperature solid oxide fuel cells. Perovskite composite cathode material La0.3Sr0.7Fe0.4Ti0.6O3‐δ (LSFT) is synthesized using the sol–gel method. Graphene oxide (GO) is integrated in 1 and 1.5 wt.% into the perovskite LSFT cathode to use as a cathode for low‐temperature solid oxide fuel cell (LT‐SOFC). Crystal structure analysis is studied by XRD and the crystalline size of samples is determined in the range of 103–73 nm. SEM analysis is used to characterize homogeneous and porous morphology. The FTIR spectral analysis is examined for proposed nanocomposite cathode materials. The electrical conductivities are carried out by four probe method in air atmosphere in the temperature range 300–600 °C and enhanced conductivity is obtained 7 Scm−1 for LSFT‐1.5 wt.% GO sample. For the same sample, a minimum value of area‐specific resistance (ASR) of 0.02 Ωcm2 is obtained. The performance of three‐layer fuel cells is tested by supplying H2 fueled at the anode and oxygen at the cathode terminal of the cell and peak power density is determined to be 362 mWcm−2 for GO incorporated fuel cell. The prepared cathode can be proposed as a potential candidate for low‐temperature solid oxide fuel cells.
A Thermoresponsive Lead‐Free Organic‐Inorganic Hybrid Perovskite as a Dielectric Switch
Authors: Ou‐yang Yuliang , Li Lutao , Wang Chen , Zou Guifu , Huang Chao‐Ran 
Published: December 2023

AbstractThermochromic perovskites, renowned for their tunable bandgap, high absorption coefficient, and reversible color changes, emerge as promising candidates for applications in smart windows. These advancements not only have the potential to enhance occupant comfort but also contribute significantly to reducing energy consumption in buildings. Here, we present a two‐dimensional lead‐free organic‐inorganic hybrid perovskite [Cyclobutylammonium]2CuCl4 which shows phase transitions from C2/c to P21/c to P21/c space group at 319.5 K and 348.8 K, respectively. Accompanying these transitions is a fascinating, reversible thermochromic behavior that is dependent on the phase structure. This behavior manifests as a vibrant sequence transitioning from yellow to brown and finally to a slightly dark brown. Most importantly, the demonstrated ability to switch stably between high and low dielectric states indicates the enormous potential of this material as a dielectric switch. This non‐toxic thermoresponsive perovskite, characterized by its appropriate transition temperatures, reversible phase structure‐dependent thermochromism, and stable dielectric switching behavior, is expected to generate significant interest within the fields of thermoresponsive and dielectric switching materials. The integration of these features not only positions this perovskite as a noteworthy subject of scientific inquiry but also opens avenues for practical applications in diverse fields.