bluuebunny/crossref_metadata_2025_split huggingface dataset:
ALLFTD Mobile App Balance and Finger Tapping Tasks: Task Description and Initial Reliability and Validity Findings
Authors: Wise Amy B , Clark Annie L , Taylor Jack C , Heuer Hilary W. , Mester Carly T. , Rao Meghana , Brushaber Danielle , Boeve Bradley F. , Forsberg Leah K. , Kramer Joel H. , Rosen Howard J. , Boxer Adam L , Staffaroni Adam M. 
Published: December 2022

AbstractBackgroundMotor disturbances are common in patients with a variety of neurodegenerative and neurological syndromes, such as Parkinson’s disease and Frontotemporal Dementia (FTD). Accurately quantifying motoric changes could enable earlier detection and monitoring of these syndromes, and remote quantification may allow for more frequent assessments and may improve access to research for underrepresented and geographically dispersed participants. With these benefits in mind, investigators from the ALLFTD consortium developed smartphone tests of balance and finger tapping speed. Here we present preliminary test‐retest reliability and associations with gold standard tests.MethodThe tasks were analyzed in two independent samples. The first was an in‐person cohort of healthy older adults (n = 7), mild cognitive impairment (MCI, n = 1) and FTD (n = 3) who completed the smartphone standing/balance and finger tapping tests (FTT) twice in person. The second sample included 31 ALLFTD participants with a range of clinical presentations (healthy older adults [n = 11], FTD [n = 5], MCI [n = 2], unknown [n = 13]) who were asked to complete the balance test three times over two weeks at home. The primary outcomes were total taps for the FTT and root mean squared acceleration for the balance test. Test‐retest reliability was calculated using an intraclass correlation coefficient (ICC); given the small sample size, outliers (n = 6) were removed from the balance test. We tested the association of smartphone FTT with the gold standard mechanical FTT and the balance task with the CDR®+NACC‐FTLD‐SB (disease severity) using Spearman’s correlations. A Wilcoxon‐sign rank test compared participants with motor features on the Progressive Supranuclear Palsy Rating Scale (PSPRS>0) to those without (PSPRS = 0).ResultThe smartphone FTT showed good test‐retest reliability (ICC = 0.78) and a strong correlation (r = 0.8,p<0.05) with mechanical FTT. The test‐retest reliability for the balance task was excellent for the remote sample (ICC = 0.97) and in‐person (ICC = 0.89) samples. In the remote sample, greater acceleration was correlated with higher CDR®+NACC‐FTLD‐SB (r = 0.7,p = 0.003), and participants with motor features on the PSPRS had higher acceleration than those without (W = 11,p = 0.04).ConclusionThese findings provide preliminary support for the reliability and validity of the ALLFTD Mobile App tests of motor function. Replication in a larger sample is required.
Cognitive Correlates of the No Practice Effects (NPE) Battery: Factor Analyses from the Novel Cognitive and Functional Measures for Alzheimer’s Disease Prevention Trials (NoMAD)
Authors: Kim Hyun , Lee Seonjoo , Bell Sophie A. , Levine Alina , Carlson Scott , Gordon Marc L. , Devanand Davangere P. , Rivera Andres M. , Brickman Adam M. , Harvey Philip D. , Schneider Lon S. , Goldberg Terry E. 
Published: December 2022

AbstractBackgroundThe No Practice Effects (NPE) battery is a novel set of neuropsychological measures designed to assess important cognitive domains and have robust psychometric properties for use in preclinical and early‐stage Alzheimer’s disease clinical trials. The current study used exploratory factor analysis to examine cognitive domains in the NPE battery. We further examined the association between identified cognitive domains with demographic characteristics, brain imaging metrics, and genetic risk markers for Alzheimer’s disease.MethodsA total of 116 older adults who are cognitively healthy or have early mild cognitive impairment (eMCI) (mean age 70.35 ± 6.53, 62.9% women) and have baseline cognitive assessments were included. The NPE battery contains seven primarily computerized tests of memory and attention. We conducted an exploratory factor analysis using an oblique rotation to identify different cognitive domains within the NPE, then composite scores were calculated for each domain. Simple correlation analyses were conducted to examine the association between these composite scores and demographic characteristics. The multiple regression analyses were performed to examine the association between composite scores and AD risk markers.ResultsThe exploratory factor analysis produced three factors within the NPE battery corresponding to 1) Cognitive Control/Executive Functions (including Letter and Category Verbal Fluency, Brown‐Peterson Paradigm, Digit Symbol Substitution Test, Letter‐Number Span, and N‐Back); 2) Response Monitoring (Recognition Memory Test [RMT] learning and correctly rejected recognition items) reflecting encoding process and post‐recollection cognitive monitoring; and 3) Recall/Retention (RMT total recall and hits on recognition items) that may be considered a “memory consolidation” factor. Greater performance on Response Monitoring was associated with younger age (r2 = ‐0.27, P = 0.004), higher education level (r2 = 0.29, P = 0.002), and APOE4 genotype (B = ‐0.27, SE = 0.13, P = 0.04). Recall/Retention was positively associated with the thickness of the entorhinal cortex (B = 0.58, SE = 0.28, P = 0.04), but not hippocampal or parahippocampal volumes. The general composite score encompassing all tests was associated with age (r2 = ‐0.29, P = 0.002), education (0.28, P = 0.003), and APOE4 (B = ‐0.25, SE = 0.10, P = 0.01).ConclusionThese results provide preliminary evidence that the NPE battery identifies domains characteristic of cognition. These cognitive domains were associated with demographic factors, such as age and education, along with APOE4 genotype, and brain structural measures.
Investigating the role of neuronal hyperactivity in stress susceptibility and brain beta‐amyloid deposition
Authors: Rogers Annika , Sharp Elizabeth , Razlighi Ray , Oh Hwamee 
Published: December 2022

AbstractBackgroundBoth animal and human literature have suggested a relationship between stress responses and an increased susceptibility to extracellular beta‐amyloid (Aβ) plaque aggregation, one of the pathological features of Alzheimer’s Disease (AD), as well as clinical symptoms of AD. Despite this evidence, a neuro‐mechanistic pathway that underlies the relationship between the psychological stress response and brain Aβ pathology remains poorly understood. We examined the hypothesis that increased stress responses are associated with neuronal hyperactivity and increased brain Aβ deposition along the spectrum of AD.MethodWe included 35 Cognitively Normal (CN) and 21 Significant Memory Concern (SMC) individuals and 81 patients with Mild Cognitive Impairment (MCI), and 29 AD patients from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Neuropsychiatric Inventory (NPI‐Q) total scores were used to indicate stress responses. The amplitude of low frequency fluctuations (ALFF) was calculated using resting‐state fMRI (rsfMRI) scans as a measure of neuronal activity. AV45‐SUVR measures were downloaded from the ADNI study. In SPM12, general linear models were performed on normalized ALFF maps to examine the associations of stress responses and brain Aβ deposition with neuronal activity, while controlling for age, sex, and APOE4 carrier status.ResultNPIQ scores were significantly associated with brain Aβ indices across the entire cohort spanning from cognitively normal (CN) older adults to AD patients. The CN group exhibited significant increases in ALFF in the anterior cingulate, caudate, and inferior occipital cortices in relation to increased NPI‐Q scores, while AD participants exhibited decreased ALFF in multiple regions including medial and lateral frontal cortices. Moreover, with higher brain Aβ load, CN participants showed increased ALFF in medial and lateral frontal cortices, while AD participants showed decreased ALFF in medial frontal, temporo‐parietal junction, and inferior parietal cortices.ConclusionThese results indicate a potential link between heightened stress responses and increased susceptibility to the development of AD pathologies through neuronal hyperactivity, especially in the early stages of AD. These findings provide neural mechanisms underlying the relationship between stress as a risk factor for AD by highlighting the role of neuronal hyperactivity in this association, while validating the use of rsfMRI for these analyses.
Practice makes imperfect: Positive correlation between practice and implicit distraction in asymptomatic individuals with Alzheimer’s disease pathology
Authors: Hung Shao‐Min (Sean) , Wu Daw‐An , Shimojo Shinsuke , Arakaki Xianghong 
Published: December 2022

AbstractBackgroundOur recent research showed that cognitively healthy older participants with higher biochemical risk to develop Alzheimer’s disease were more distracted by an incompatible and implicit visual stimulus, which was not observed in low‐risk older participants. This finding shed light on using psychophysical experiments to early identify high‐risk older participants. Here we further examined the role of practice based on our findings in the young healthy participants where implicit distracting information processing was enhanced after practice. We expected the effect of practice on processing the implicit distractor in high‐risk and low‐risk participants would bifurcate.MethodsCognitively healthy (CH) participants were recruited from the local community, consisting of two subgroups based on cerebrospinal fluid (CSF) proteins: with normal beta amyloid42/total tau ratio (CH‐NAT, low‐risk, n = 17) or pathological beta amyloid42/total tau ratio (CH‐PAT, high‐risk, n = 19). Their age, gender, education year, and days between the two sessions were all comparable. A task‐switching Stroop task was implemented. Each trial contained two stimuli, and participants had to name the color or word of a colored word for each stimulus with button press. Only correctly responded trials (correct responses to both stimuli in the trial) were analyzed. Below we reported the performance on the second stimulus (target).ResultsIn general, participants showed a significant practice effect over the two sessions. Their reaction times (RT) decreased by 6.19 % (3.04 %), and accuracy rates (ACC) increased by 6.09 % (1.04 %). These results showed evident improvement on performance.Critically, we further investigated the relationship between the practice effect and the subliminal distractor effect. We found a significant positive correlation in high‐risk participants between the practice effect and the strength of subliminal RT interference (p = 0.03). That is, the more RT decrease observed in a high‐risk individual, the stronger interference was found. Such a linkage was not found in low‐risk participants (p > 0.05).ConclusionOur results clearly show that high‐risk and low‐risk asymptomatic older participants operate on different cognitive schemes to process implicit distracting sensory information. Intriguingly, better practice effect is correlated with stronger implicit distraction only in high‐risk participants.
Topline Results of EXERT: Can Exercise Slow Cognitive Decline in MCI?
Authors: Baker Laura D. , Cotman Carl W. , Thomas Ronald , Jin Shelia , Shadyab Aladdin H. , Pa Judy , Rissman Robert A. , Brewer James B. , Zhang Jing , Jung Youngkyoo , LaCroix Andrea Z. , Messer Karen , Feldman Howard H. 
Published: December 2022

AbstractBackgroundThe EXERT trial (NCT02814526) was a Phase 3, multicenter, randomized single‐blind study that examined the effects of regular exercise on cognition and other measures of brain function in a planned sample of 300 older adults with amnestic mild cognitive impairment (MCI).MethodThe Alzheimer’s Disease Cooperative Study (ADCS) coordinated the trial, in partnership with Wake Forest and the YMCA of the USA. Participants were randomized to moderate intensity aerobic training (AX), or to stretching, balance and range of motion (SBR) for 18 months. In the first 12 months, exercise was supervised 2x/week and completed independently 2x/week. All exercise was unsupervised in Months 13‐18. Outcomes assessments were completed at baseline and every 6 months. The primary endpoint was 12‐month change from baseline on the ADAS‐Cog‐Exec, a validated measure of global cognitive function. In addition, 12‐month changes in the ADAS‐Cog‐Exec and CDR‐SB were compared for EXERT intervention groups relative to other cohorts to estimate effects of intervention versus no intervention (i.e., “Usual Care”).Result296 participants were enrolled, and over 31,000 exercise sessions were completed during the first 12 months. Attendance remained high (AX: 81%; SBR: 87%), and >60% of participants reported continued exercise through the pandemic. Neither the AX group nor the SBR group showed 12‐month declines on the ADAS‐Cog‐Exec and CDR‐SB. There were no significant treatment differences between AX and SBR on these outcomes. In the Usual Care analysis comparing ADNI‐1 and EXERT participants matched on key variables (demographics, baseline cognitive function, APOE4), ADNI‐1 MCI participants showed the expected 12‐month decline on the ADAS‐Cog‐Exec, but the EXERT AX and SBR groups did not (ADNI‐1 vs. AX: p = 0.012; vs. SBR: p = 0.00049).ConclusionGlobal cognitive function did not change over 12 months of follow‐up for MCI participants in EXERT, suggesting that both the AX and SBR interventions may have stalled cognitive decline. EXERT is the longest exercise trial conducted in MCI to date, and greater ‘volume’ of exercise may have provided more protection, regardless of exercise intensity. Both groups received equal amounts of weekly socialization, which may have contributed to this protection. Our results are noteworthy given that trial was conducted during the COVID‐19 pandemic.
The case for low‐level BACE1 inhibition for the prevention of AD
Authors: Watkins Elyse 
Published: December 2022

AbstractAlzheimer disease (AD) is the most common cause of dementia in older individuals (>65 years) and has a long presymptomatic phase. Preventive therapies for AD are not yet available, and potential disease‐modifying therapies targeting amyloid‐β plaques in symptomatic stages of AD have only just been approved in the United States. Small‐molecule inhibitors of β‐site amyloid precursor protein (APP)‐cleaving enzyme 1 (BACE1; also known as β‐secretase 1) reduce the production of amyloid‐β peptide and are among the most advanced drug candidates for AD. However, to date all phase II and phase III clinical trials of BACE inhibitors were either concluded without benefit or discontinued owing to futility or the occurrence of adverse effects. Adverse effects included early, mild cognitive impairment that was associated with all but one inhibitor; preliminary results suggest that the cognitive effects are non‐progressive and reversible. These discontinuations have raised questions regarding the suitability of BACE1 as a drug target for AD. In this talk, I discuss the status of BACE inhibitors and suggest ways in which the results of the discontinued trials can inform the development of future clinical trials of BACE inhibitors and related secretase modulators as preventative therapies. We also propose a series of experiments that should be performed to inform ‘go‐no‐go’ decisions in future trials with BACE inhibitors and consider the possibility that low levels of BACE1 inhibition could avoid adverse effects while achieving efficacy for AD prevention.
Relationship between beta‐amyloid (Ab) plaque reduction and clinical benefit: the rationale for aducanumab approval
Authors: Wang Yaning 
Published: December 2022

AbstractBackgroundAducanumab was approved in 2021 by the US FDA under the accelerated approval pathway. However, the Office of Clinical Pharmacology at FDA recommended the regular approval based on three key findings.MethodExposure‐response analyses were conducted to quantify the relationship between aducanumab longitudinal exposure and responses (standardized uptake values ratios for beta amyloid and various clinical endpoints) in all clinical trials. To explain the difference between aducanumab and other compounds with negative results in the past, publicly available data were combined with the aducanumab data to demonstrate the relationship between amyloid reduction and clinical endpoint improvement across multiple compounds with similar mechanism of action. The probability to observe the overall positive findings in the aducanumab program was quantified under the assumption that aducanumab is ineffective.ResultsPositive exposure‐response (disease progression) relationship for multiple clinical endpoints from all clinical trials was identified. Positive exposure‐amyloid reduction relationship was established. Consistent amyloid reduction‐clinical endpoint improvement relationship across multiple compounds was observed. If aducanumab is assumed to be ineffective, it is extremely impossible to observe the overall positive findings in the aducanumab program. These results provided convincing evidence to support aducanumab’s effectiveness.ConclusionFDA made the right decision for millions of Alzheimer patients. The observed clinical benefit from aducanumab treatment is clinically meaningful.
Photocatalytic Generation of Hydrogen Radical (H⋅) with GSH for Photodynamic Therapy
Authors: Peng Jinlei , Du Ke , Sun Jian , Yang Xianli , Wang Xia , Zhang Xiaoran , Song Gang , Feng Fude 
Published: December 2022

AbstractAs a reactive hydrogen species, the hydrogen radical (H⋅) scarcely sees applications in tumor biological therapy due to the very limited bio‐friendly sources of H⋅. In this work, we report that TAF can act as an organic photosensitizer as well as an efficient photocatalytic H⋅ generator with reduced glutathione (GSH) as a fuel. The photoactivation of TAF leads to cell death in two ways including triple amplification of oxidative stress via ferroptosis‐apoptosis under normoxia and apoptosis through biological reductions under hypoxia. TAF presents excellent biosafety with ultrahigh photocytotoxicity index at an order of magnitude of 102–103 on both normoxic and hypoxic cells. The in vitro data suggest that H⋅ therapy is promising to overcome the challenge of tumor hypoxia at low doses of both photocatalyst and light. In addition, the capability of near‐infrared two‐photon excitation would benefit broad biological applications.
Porous Materials for Water Purification
Authors: Song Yanpei , Phipps Joshua , Zhu Changjia , Ma Shengqian 
Published: December 2022

AbstractWater pollution is a growing threat to humanity due to the pervasiveness of contaminants in water bodies. Significant efforts have been made to separate these hazardous components to purify polluted water through various methods. However, conventional remediation methods suffer from limitations such as low uptake capacity or selectivity, and current water quality standards cannot be met. Recently, advanced porous materials (APMs) have shown promise in improved segregation of contaminants compared to traditional porous materials in uptake capacity and selectivity. These materials feature merits of high surface area and versatile functionality, rendering them ideal platforms for the design of novel adsorbents. This Review summarizes the development and employment of APMs in a variety of water treatments accompanied by assessments of task‐specific adsorption performance. Finally, we discuss our perspectives on future opportunities for APMs in water purification.
Altering Oxygen Binding by Redox‐Inactive Metal Substitution to Control Catalytic Activity: Oxygen Reduction on Manganese Oxide Nanoparticles as a Model System**
Authors: Wu Yi‐Hsuan , Mehta Harshit , Willinger Elena , Yuwono Jodie A. , Kumar Priyank V. , Abdala Paula M. , Wach Anna , Kierzkowska Agnieszka , Donat Felix , Kuznetsov Denis A. , Müller Christoph R. 
Published: December 2022

AbstractEstablishing generic catalyst design principles by identifying structural features of materials that influence their performance will advance the rational engineering of new catalytic materials. In this study, by investigating metal‐substituted manganese oxide (spinel) nanoparticles, Mn3O4:M (M=Sr, Ca, Mg, Zn, Cu), we rationalize the dependence of the activity of Mn3O4:M for the electrocatalytic oxygen reduction reaction (ORR) on the enthalpy of formation of the binary MO oxide, ΔfH°(MO), and the Lewis acidity of the M2+ substituent. Incorporation of elements M with low ΔfH°(MO) enhances the oxygen binding strength in Mn3O4:M, which affects its activity in ORR due to the established correlation between ORR activity and the binding energy of *O/*OH/*OOH species. Our work provides a perspective on the design of new compositions for oxygen electrocatalysis relying on the rational substitution/doping by redox‐inactive elements.
Fluorescence turn‐off and turn‐on sensors of Zn2+ based on π‐conjugated poly(aryleneethynylene)s comprising alloxazine‐6,9‐diyl and 2,7‐diethynylene‐9,9‐dialkylfluorene units
Authors: Yamaguchi Isao , Yoshizawa Soma , Wang Aohan 
Published: December 2022

Abstractπ‐Conjugated poly(aryleneethynylene)s, polymer‐1 comprising alloxazine‐6,9‐diyl and 2,7‐diethynylene‐9,9‐dihexylfluorene units and polymer‐2 comprising alloxazine‐6,9‐diyl and 2,7‐diethynylene‐9,9‐bis(hexaethylene glycol monomethyl ether)fluorene units, were synthesized via Pd‐complex‐catalyzed condensation reactions. The Mn values of polymers 1 and 2 were 5200 and 8100, and Mw values were 24,900 and 69,700, respectively. The onset wavelengths of the polymers were longer wavelength than that of the monomer in the UV–vis spectra, confirming the π‐conjugated system along the polymer chain. The photoluminescence (PL) of the polymers decreased with the addition of Zn2+ until an equimolar amount and then increased upon the addition of an excess amount of Zn2+, which enabled the detection of Zn2+ over a wider concentration range (10−6–10−4 M) than those of the previously reported Zn2+ sensors. The PL intensity upon the addition of excess Zn2+ was greater in polymer‐2 than in polymer‐1 because the Zn2+‐alloxazine complex in polymer‐2 was stabilized by its interaction with the oligoether side chain. The difference in the PL response of the polymers to metal ions such as Cu+, Cu2+, and Zn2+ was analyzed using the Stern–Volmer and Benesi–Hildebrand methods.