bluuebunny/crossref_metadata_2025 huggingface dataset:
Pupillary responses as a biomarker of early risk for Alzheimer’s disease: Association with tau not beta‐amyloid
Authors: Granholm Eric L. , Elman Jeremy A. , Galasko Doug R. , Kremen William S. , Salmon David P. , Holden Jason , Delay Christophe , Macomber Alyssa , Link Peter , Bondi Mark W.
Published: February 2022

Background

We examined pupillary responses as a novel biomarker of early risk for Alzheimer’s disease (AD). Pupil dilation recorded during cognitive tasks provides a biomarker of the extent of cognitive effort required to achieve a given test score. Greater dilation indicates greater effort. Test scores decline when capacity to compensate is exceeded, so individuals allocating more effort are likely closer to maximum compensatory capacity and at higher risk for decline. We previously found greater pupil dilation in individuals with mild cognitive impairment (MCI) relative to cognitively‐normal (CN) controls. Pupillary responses reflect neuromodulatory activity in the locus coeruleus (LC), and studies implicate the LC as an early site of AD degenerative changes, especially tauopathy. The present study, therefore, examined whether greater pupil dilation (compensatory cognitive effort) on the digit span task was associated with greater tau biomarker levels.

Method

Pupillary responses were recorded using a Tobii pupillometer during the digit span task and CSF biomarkers of AD (Aβ40; Aβ42 and p‐tau181) were collected in CN (N=37) and MCI (N=17) participants. Three trials at each span length (3‐9 digits) were administered until reaching max span (highest span with at least one correct trial).

Result

In the total sample, greater p‐tau was significantly associated with greater pupil dilation during the digit span task. However, pupil dilation was not significantly associated with beta‐amyloid. Importantly, performance (max span or total accuracy of digit recall) was not significantly correlated with pupil dilation or any of these biomarkers, so pupil dilation, but not performance, was associated with p‐tau biomarker risk.

Conclusion

Greater tau deposition, but not beta‐amyloid, was associated with greater compensatory cognitive effort during the digit span task. This simple 5‐min pupil dilation task holds promise as a novel marker of early AD risk specifically linked to tauopathy and impaired functionality of the LC years prior to cognitive decline and diagnosis.
Memory and executive function are associated with distinct patterns of regional cerebral perfusion in dementia‐free APOE‐ε4 carriers and non‐carriers
Authors: Dutt Shubir , Yew Belinda , Li Yanrong , Gaubert Aimee , Ho Jean K , Jang Jung Yun , Blanken Anna E , Sible Isabel J , Marshall Anisa J , Kapoor Arunima , Shao Xingfeng , Wang Danny JJ , Nation Daniel A
Published: February 2022

Background

The primary genetic risk factor for Alzheimer’s disease is the apolipoprotein ε4 (APOE‐ε4) allele, which confers significant risk for early symptom onset and future dementia. Prior studies have examined links between memory function and medial temporal perfusion in APOE‐ε4 carriers and non‐carriers, but findings have been mixed regarding the direction of relationships. Additionally, prior work has not examined whether other cognitive domains, such as executive function, are similarly associated with functionally relevant regional perfusion (i.e., in frontal regions). The present study aimed to 1) clarify the relationship between medial temporal perfusion and memory performance and 2) examine novel links between executive function and frontal perfusion in APOE‐ε4 carriers and non‐carriers.

Method

Dementia‐free older adults recruited from the community were classified as APOE‐ε4 carriers (n=18) or non‐carriers (n=30) via genotype analysis. We used pseudocontinuous arterial spin labeling MRI to quantify cerebral perfusion in regions involved in memory (medial temporal) and executive function (medial frontal). Comprehensive neuropsychological testing assessed memory (Logical Memory I & II; Visual Reproduction I & II) and executive function (Stroop color‐word interference; Trail making tests A & B, category fluency). Multiple linear regression, modeled separately within carriers and non‐carriers, examined associations between perfusion and cognition, with age, sex, and education as covariates.

Result

Within APOE‐ε4 carriers, medial temporal hypoperfusion was associated with worse immediate and delayed recall memory in verbal and visual paradigms. Similarly, frontal hypoperfusion was associated with worse verbal category fluency. In non‐carriers, relationships between medial temporal perfusion and memory were absent. Relationships between frontal perfusion and executive function were in the opposite direction as those observed in APOE‐ε4 carriers, with frontal hyperperfusion predicting worse Stroop color‐word, Trails A, and Trails B performance.

Conclusion

We observed positive associations between regional perfusion and corresponding cognitive domains in APOE‐ε4 carriers, while relationships were absent or negative within non‐carriers. Our findings highlight the importance of examining preclinical cerebrovascular dysfunction in relation to cognition in individuals at risk for progression to dementia. Future longitudinal studies will be needed to further examine the value of perfusion, cognition, and APOE‐ε4 carrier status in predicting future decline.
Engaging Vietnamese Americans in research on aging and dementia
Authors: Meyer Oanh L , Nguyen Julia Phuong , Nam Bora , Nguyen Khue , Zhu Jeanette , Vuong Quyen , Bang Joon , Hinton Ladson , Tsoh Janice Y , Park Van Ta
Published: February 2022

Background

Vietnamese Americans are a large Asian American group in the U.S. and at high risk for health disparities, partially due to their limited English proficiency, low socioeconomic status, history of war and trauma, and a lack of culturally and linguistically appropriate care. As this relatively recent refugee population continues to age in the U.S., it is important to engage them in research around Alzheimer’s disease and related dementias (ADRD). Yet few studies have examined their perceptions of aging, dementia, and ADRD research participation. This qualitative study examined the perceptions of Vietnamese in Northern and Southern California, the state with the largest population of Vietnamese Americans in the U.S.

Method

We conducted three focus groups with a total of 20 Vietnamese individuals in both Vietnamese and English. The focus group guide assessed participants’ attitudes and experiences with research participation, perceptions of ADRD and aging, and insights into registry outreach and recruitment. There were nine women, and the mean age was 40 years, SD = 17.74 (range 18‐73). Participants consisted of key stakeholders including community leaders, ADRD caregivers, and community members.

Result

Several themes emerged from the analyses, including (1) Motivations to participate in research to gain knowledge: (a) for oneself, (b) for family’s benefit, and (c) for the Vietnamese American community as a whole; (2) The necessity of trustworthy and credible individuals/spokespersons to promote the research initiative; (3) Recruitment strategies that are age‐specific and culturally appropriate, and (4) Importance of monetary incentives.

Conclusion

Results highlight key issues that are important to Vietnamese Americans’ participation in aging and dementia research. Practical implications of these results will be discussed.
Simulation as an innovative approach in dementia caregiver education: A literature review
Authors: Chan Hoi Man , Wong Cho Lee
Published: February 2022

Background

Simulation has well been used for training healthcare professional; however, such innovative approach in dementia caregiver education is still at infancy. This study aims to review the application of simulation in the education of dementia family caregiver regarding the simulation modality, skills trained and outcomes.

Method

Keywords including “caregiv*”, “simulation” and “caregiver education” were used for searching in PubMed, CIHNAL, Medline, Psyinfo and Embase databases. Publications were searched up to 2021 and 7 studies were reviewed.

Result

Studies were conducted in US, Netherland, Canada and South Korea of sample size ranging from 28 to 264. Study designs included RCT, quasi experimental and non‐experimental. Virtual reality was employed to enhance empathy and competency of caregivers; simulated patient (SP) was employed to enhance communication skill and problem‐solving technique; low‐fidelity simulator (Dementia LiveTM) was employed to enhance empathy and problem solving. Outcomes included improvement in empathy, caregiving competency and decreased use of emotion‐focused and avoidance‐focused coping. None of the studies provided detailed simulation design.

Conclusion

Simulation as an innovative approach may inform nursing intervention in dementia care. Nurses could incorporate simulation into psychoeducation to enhance dementia family caregivers’ self‐efficacy. Communication skill, problem‐solving technique and behavioral problem can be addressed through therapeutic simulation with the use of SP methodology (Sadvoy et al, 2020). Scenario design should be person‐centered and simulation design should be stringent. Experimental studies are urged to determine the effectiveness.
Free water in T2 FLAIR white matter hyperintensity lesions
Authors: Yu Xiaowei , Scheel Norman , Zhang Lu , Zhu David C. , Zhang Rong , Zhu Dajiang
Published: February 2022

Background

White matter (WM) free water (FW) is likely associated with cerebral small vessel disease (CSVD). FW is the fraction of unconstrained water within an image voxel, which can be estimated from diffusion‐weighted images. T2‐weighted Fluid‐Attenuated Inversion Recovery (FLAIR) white matter hyperintensity (WMH) is a widely used index to assess the damages caused by CSVD. It is critical to characterize how FW content is altered in WMH lesions. In this work, we proposed a data processing framework to assess FW distributions in WMH and normal‐appearing WM as well as in different WM fiber tracts.

Method

Single‐shell diffusion‐weighted image (SS‐DWI) and T2 FLAIR image data of 133 cognitively normal (CN) adults (Table 1) were obtained from the ADNI dataset (http://adni.loni.usc.edu). FW maps were generated from SS‐DWI images using the DIPY software package (https://dipy.org/). WMH lesions were identified with the lesion segmentation toolbox implemented in SPM. We co‐registered FW and WMH maps of individual subjects in the MNI space. Then we derived group WM fiber tracts using the tract‐based spatial statistics (TBSS). Finally, we examined the localization of WMH and FW in the major WM tracts.

Result

Figure 1 shows the FW map, FLAIR image, and WMH lesion from a representative subject. Figure 2 shows group average and individual FW distributions in WMH and normal‐appearing WM. Two sample T‐Test found that FW content in WMH is significantly higher than that in normal‐appearing WM (mean FW and standard deviation FW in WMH are 0.430 and 0.112, mean FW and standard deviation FW in normal‐appearing WM are 0.203 and 0.06, P < 1×10‐30). TBSS based analysis showed that: 1) WMH lesions are mainly located in the corona radiata, posterior thalamic radiation, tapetum, superior fronto‐occipital fasciculus, superior longitudinal fasciculus, corpus callosum, and sagittal stratum; 2) Compared with mean FW in normal‐appearing WM, elevated FW content is mainly at the fornix, tapetum, cingulum hippocampus, superior fronto‐occipital fasciculus, corpus callosum, sagittal stratum, and posterior thalamic radiation.

Conclusion

We developed an image processing pipeline to estimate FW changes in WMH lesions and normal‐appearing WM. Free water content is elevated in WMH lesions, which is likely driven by CSVD.
A gatekeeper for amyloid status based on FDG‐PET and genetic risk in patients with mild cognitive impairment
Authors: Doering Elena , Hönig Merle C , Bischof Gerard N , van Eimeren Thilo , Drzezga Alexander
Published: February 2022

Background

Amyloid‐β (Aβ) accumulation is a characteristic hallmark for Alzheimer’s disease (AD), which is known to be modified by the APOE genotype. Current diagnostic recommendations for AD include the assessment of amyloid status (A‐status: Aβ+ or Aβ‐) through positron‐emission‐tomography (PET) or invasive lumbar puncture. Amyloid‐PET imaging is costly and currently not generally covered by insurance companies. FDG‐PET, in contrast, is comparably inexpensive, commonly available and often employed to assess extent and localization of neurodegeneration (N‐status) in patients with (mild) cognitive impairment (MCI). We aimed to explore, whether advanced machine learning allows for an approximation of the A‐status from FDG‐PET data and APOE genotype, which could make these biomarkers a gatekeeper in deciding on the need for additional amyloid testing.

Method

Models for the approximation of the A‐status were trained for APOE4 carriers (APOE‐c) and non‐carriers (APOE‐nc) in parallel. We included 574 FDG‐PET scans of patients with MCI from the ADNI cohort (185 Aβ‐APOE4‐nc; 107 Aβ+APOE4‐nc; 46 Aβ‐APOE4‐c; 236 Aβ+APOE4‐c). A‐status was determined from established cut‐off values for cerebrospinal fluid and/or amyloid‐PET. Using SPM12, regional FDG‐PET standardized uptake value ratios were extracted from spatially normalized scans for 90 brain regions. Different machine learning classifiers were trained on 70% of the data, while the remaining 30% (n=85 (APOE4‐c); n=88 (APOE4‐nc)) were reserved for testing. APOE‐c and ApoE‐nc models were trained to maximize precision of Aβ‐ and Aβ+, respectively (“relevant instances”), as well as the percentage of relevant instances identified by a classifier (“recall”) by means of the F1/10‐score. Finally, we estimated the contribution of individual brain regions towards classification performance with permutation importance.

Result

In the test set, amyloid status was predicted with a precision of 85% (APOE4‐c) and 87% (APOE4‐nc) and a recall of 93% (APOE4‐c) and 58% (APOE4‐nc). Patterns of neurodegeneration in temporal and frontal (APOE‐nc) and temporo‐parietal regions (APOE‐c) most heavily influenced the classification process (see Figure 1).

Conclusion

We propose a highly precise and biologically plausible gatekeeper for amyloid status in MCI patients with varying genetic risk using FDG‐PET. Further validated, our models could serve to reduce the number of patients requiring amyloid testing to determine AD‐related etiology of ongoing neurodegeneration.
Reductions in biomarkers of Alzheimer’s disease pathophysiology following treatment with aducanumab were associated with slowing in clinical decline
Authors: Rajagovindan Raj , Chen Tianle , Nisenbaum Laura , Tian Ying , Muralidharan Kumar Kandadi , Dent Gersham , He Ping , Castrillo‐Viguera Carmen , Haeberlein Samantha Budd
Published: February 2022

Background

Alzheimer’s disease (AD) is characterized by the accumulation of amyloid beta (Aβ) and tau in the brain. Aducanumab is a human monoclonal antibody that selectively targets aggregated forms of Aβ. In clinical studies, aducanumab treatment resulted in dose‐ and time‐dependent reduction in Aβ levels accompanied by slowed clinical decline.

Method

Participants in the Phase 1b PRIME study (NCT01677572) were randomized to receive aducanumab (1, 3, 6, or 10 mg/kg [fixed‐dose or titrated]) or placebo every 4 weeks (q4w). The effects of aducanumab on clinical endpoints and amyloid positron emission tomography (PET) composite standard uptake value ratio (SUVR) were evaluated at the end of randomization (Week 54).

In the Phase 3 EMERGE (NCT02484547) and ENGAGE (NCT02477800) studies, participants were randomized (1:1:1) to received high‐dose aducanumab (10 mg/kg), low‐dose aducanumab (3 mg/kg), or placebo q4w. At Week 78, the effects of aducanumab on clinical endpoints were assessed; the effects on AD biomarkers were assessed in PET and CSF substudies. In the EMERGE and ENGAGE substudies, participant‐level correlations between change from baseline in clinical measures (measured by CDR‐SB, MMSE, ADAS‐Cog 13, and ADCS‐ADL‐MCI) and change from baseline in amyloid PET SUVR or CSF biomarkers (p‐tau and t‐tau) at Week 78 were examined. The same analysis between clinical decline (measured by CDR‐SB and MMSE) and change in amyloid PET SUVR was investigated in PRIME at Week 54. Group‐level correlation between treatment effect on Aβ levels as measured by PET and clinical decline was conducted across all 3 studies.

Result

Findings from EMERGE suggest that reduction in AD biomarker levels (amyloid PET, CSF p‐tau, and CSF t‐tau) following treatment with aducanumab are associated with slowing in cognitive decline. Analyses from PRIME are supportive of these findings. In ENGAGE, in which a clinical treatment effect of aducanumab was not observed, correlations were less apparent. However, group‐level analyses based on data from PRIME, EMERGE, and ENGAGE demonstrated a correlation between aducanumab treatment effect on amyloid pathology and clinical measures.

Conclusion

The correlation analyses between biomarkers and clinical measures provide evidence that aducanumab‐induced reduction in biomarkers of AD disease pathophysiology is associated with reduced clinical decline.
Methodologies used to study the effectiveness of social robots in long‐term and community care settings
Authors: Asl Aysan Mahmoudi , van der Roest Henriëtte G , Ulate Mauricio Molinari , Martin Manuel Angel Franco
Published: February 2022

Background

In a search for innovative dementia care strategies, a new research field has been dedicated to design social robots for older adults with cognitive impairments and dementia in order to promote their quality of life through communication and social interactions. Although the results are promising, the quality of studies on effectiveness of social robots in elderly adults is still low due to several methodological limitations (1). Therefore, we aimed to review the methodologies used so far for conducting studies with social robots in long‐term and community care settings with people with dementia and elderly adults.

Method

Searches in PubMed, Web of Science, PsycInfo, and Cinahl yielded 33 studies included in the final review after applying inclusion and exclusion criteria. Reviews were conducted by two authors independently.

Result

Across 33 papers, 23 different social robots were examined on elderly adults and PwD, investigating acceptability, usability and effectiveness. A variety of study designs such as RCTs, mixed methods, cross‐sectional, cohort and quasi‐experimental designs were employed. Individual and group‐based interventions took place in private households, long‐term care facilities and laboratories during single or multiple sessions. Data were collected through observation, questionnaires, interviews and physiological tests. Most revealed improvements were found in mood, engagement and participation. However, improvements in quality of life, depression and cognition were not significant.

Conclusion

Despite the promising results, due to the insufficient methodology, failures and ambitious findings remain within the many aspects of the enquiry. Appropriate experimental designs such as RCTs with large sample sizes and individual intervention sessions might be established for effectiveness studies. For acceptability/usability studies, a cohort design with long‐term intervention would serve best. We also recommend a mixed‐method of data collection for any of three effectiveness, acceptability and usability related outcomes. Multiple interaction sessions running for more than one month might help researches to draw significant results and reveal the long‐term impact of the robots. Reference: Abdi J, Al‐Hindawi A, Ng T, Vizcaychipi MPJBo. Scoping review on the use of socially assistive robot technology in elderly care. 2018;8(2):e018815.
White matter hyperintensities in the splenium of the corpus callosum predict cognitive decline in memory clinic outpatients
Authors: Garnier‐Crussard Antoine , Dauphinot Virginie , Cotton François , Teillac Achille , Cavedo Enrica , Tran Philippe , Chetelat Gaël , Salmon Pierre Krolak ,   MEMORA Group
Published: February 2022

Background

White matter hyperintensities (WMH) are very frequent in ageing and related to worse cognition. Recent studies suggest that WMH in the corpus callosum (CC) are particularly relevant in neurocognitive disorders, as they are strongly associated with lower cognitive performance, as well as amyloid and neurodegeneration biomarkers. This study examined whether WMH in subregions of the CC (genu, body, splenium) affect cross‐sectional and long‐term longitudinal (up to 5 years) cognitive performance in patients recruited from a memory clinic.

Method

This study included memory clinic outpatients from the MEMORA cohort who had a brain MRI (T1 and FLAIR scans) within 6 months of the baseline visit. QyScore® software was used for the automatic segmentation of WMH in the CC and hippocampal volumes (HP). The cross‐sectional and longitudinal relationships between regional WMH in the CC and cognitive performance, as measured with the mini‐mental state examination (MMSE), were assessed using multivariable linear regressions and mixed models.

Result

Among 236 patients included (mean age 76.2±8.8 years old; mean MMSE 23.6±4.9), 111 were diagnosed with probable Alzheimer’s disease (AD), 20 with vascular cognitive impairment (VCI), 22 with mixed AD‐VCI, 18 with another neurological disease and 65 with a subjective cognitive complaint. Cross‐sectional analyses disclosed that higher WMH in the splenium of the CC were associated with reduced MMSE (p=0.03, n=199) after adjustment for diagnosis and education. The relationship did not remain significant after adjustment for HP and total WMH. Longitudinal analyses with a follow‐up up to 5 years showed that the MMSE declined faster in patients with higher WMH in the splenium of the CC (p<0.001, n=143) after adjustment for education, diagnosis, HP and total WMH (Figure). WMH in the genu and in the body of the CC were not associated with MMSE decline (respectively p=0.92 and p=0.23, n=124, Figure).

Conclusion

WMH in the splenium of the CC were associated with cognitive decline, whereas WMH in the genu and the body were not. This study highlights the clinical relevance of posterior CC WMH in a memory clinic population.
COVID‐19 and preclinical Alzheimer disease: Driving, mobility, activity and experiences of older adults in the United States
Authors: Bayat Sayeh , Babulal Ganesh M , Widener Michael , Schindler Suzanne E , Morris John C , Mihailidis Alex , Roe Catherine M
Published: February 2022

Background

As the world grapples with the COVID‐19 pandemic, there have been widespread disruptions to everyday life due to social distancing. Older adults with Alzheimer disease (AD) are at increased risk of morbidity and mortality from COVID‐19. It is unknown how COVID‐19 affects the mobility patterns of older adults with preclinical AD. Since before the pandemic, we have been monitoring the driving behaviors of older adults, enabling us to evaluate the impact of the pandemic on individuals with and without preclinical AD.

Method

We used in‐vehicle Global Positioning System (GPS) devices to study driving behaviors of 115 older adults enrolled in the DRIVES study (aged 65+) from 1/1/2019 to 31/12/2020. The cohort included 62 individuals with preclinical AD (PreAD) and 53 without preclinical AD (CTL), as determined by cerebrospinal fluid biomarkers. All participants completed an online survey about their overall experiences during the pandemic. Using the GPS data, we determined the average monthly distance travelled, and the number of visitations to destinations categorized as food shopping, place of worship, restaurant, leisure, or health. All measures were computed monthly.

Result

oth groups experienced an approximate 40% decline in average monthly distance travelled overall after the start of the pandemic (PreAD: 1287.92 to 783.38 km vs. CTL: 1751.26 to 1053.29 km). Visits to places of worship, restaurants, leisure and health places declined by 70%, 46%, 23%, and 23% for the PreAD group, and by 48%, 31%, 48%, and 22% for the CTL group, respectively. However, the pandemic did not result in a significant decline in Food Shopping among either of the groups. Overall, compared to the CTL group, the PreAD group experienced a higher level of stress in response to the recommendations for socially distancing (p<0.01), more uncertainty about their risk of COVID‐19 (p<0.05), more decline in trips for worship (p<0.05) and less decline in trips for leisure (p<0.01).

Conclusion

Our findings indicate decreased mobility in all older adults during the pandemic, with the preclinical AD group exhibiting more decline in trips to places of worship, less decline in leisure activities, and increased stress and uncertainty in response to COVID‐19.
Tau accumulation using [18F]MK6240 PET is associated with increase in executive dysfunction in prodromal AD
Authors: Pallen Vanessa , Lussier Firoza Z. , Poltronetti Nina Margherita , Therriault Joseph , Bezgin Gleb , Arias Jaime Fernandez , Rahmouni Nesrine , Stevenson Jenna , Stevenson Alyssa , Kang Min Su , Mathotaarachchi Sulantha , Tissot Cécile , Benedet Andréa Lessa , Wang Yi‐Ting , Pascoal Tharick A. , Gauthier Serge , Rosa‐Neto Pedro
Published: February 2022

Background

Decline in executive function has been noted to precede other forms of cognitive decline in the prodromal stage of Alzheimer’s disease (Clark et al., 2011). The D‐KEFS Color‐Word Interference test (CWIT) is a cognitive test that measures executive function across several conditions. Few studies have explored the relationship between tau deposition and executive dysfunction. However, to date, no study has explored this relationship in prodromal AD. This study aimed at exploring such associations.

Method

We looked at cognitively unimpaired and impaired elderly individuals from the TRIAD cohort in Montreal, QC who underwent neuropsychological evaluations across 2 time points. In vivo tau accumulation was assessed at baseline with [18F]‐MK6240 PET. Standardized uptake value ratio was calculated 90‐110 minutes post‐injection using cerebellar grey matter as the reference region. Voxel‐wise linear regression models were applied with the rate of change of CWIT condition 3 and 4 completion times as predictor variables with tau tracer binding being the response variable. Age, sex, education, Geriatric Depression Scale score, APOEε4, diagnostic group, and amyloid‐β status were included as covariates in regression models. Results were corrected for multiple comparisons using random field theory with a cluster threshold of p < .001.

Result

A total of 105 (CN=65;MCI=36;AD=4) individuals were included in this analysis, with mean follow‐up time of neuropsychological evaluation being 15.9 months. We found that brain [18F]‐MK6240 uptake was correlated with change in D‐KEFS CWIT condition 3 and 4 completion times, with a greater pattern of association in condition 3 (inhibition). For condition 3, associations were strongest in the precuneus, posterior cingulate, and primarily right dorsal frontal and parietal regions. For condition 4 (flexibility), we found a strong association in the left temporal pole and left dorsal frontal regions.

Conclusion

These results support previous claims that tau follows a distinct regional distribution similar to that of the dorsal attention network which is related to higher order cognitive function such an inhibition and switching (Hansson et al., 2017). Additionally, given that most individuals in this study were CN or MCI, our findings suggest that tau pathology is associated with a decrease in executive function even in prodromal stages of AD.
The relationship among Aβ‐42 and p‐Tau biomarkers, functionality and cognition in patients without cognitive impairment and patients with Alzheimer’s dementia
Authors: Valu dos Santos Lorena Aline , Burgos Ivonne Carolina Bolaños , Costa Mônica Vieira , de Oliveira Hansen Erika , Dias Natália Silva , da Fonseca Aristeu Mascarenhas , Miranda Mariana Figueiredo , Miranda Millena Figueiredo , Gomes Giulia Costa , de Mattos Viana Bernardo , Bicalho Maria Aparecida Camargos
Published: February 2022

Background

Comparison between functionality and cognition in elderly patients with Alzheimer’s dementia (AD) and without cognitive impairment with positive and negative Aβ‐42 and p‐Tau biomarkers evaluated using the Luminex technique.

Method

Patients with Alzheimer’s dementia and normal cognition (control) were recruited. They were divided in two groups according to their clinical diagnosis: AD group (n=30) and control group (CTRL) (n=10). The AD group was then divided in patients with positive (n=21) and negative (n=9) Aβ‐42 and p‐Tau biomarkers. The participants were submitted to sociodemographic. The general cognition was evaluated through the following instruments: the Mini‐Mental State Examination (MMSE), semantic verbal fluency (SVF), animal fluency, short term memory, and recognition of CERAD battery, and functionality was evaluated by the Pfeffer scale. Samples from the cerebrospinal fluid (CSF) of patients were collected, processed, and stored at ‐80°C until use. The Luminex technique was then used for the Aβ‐42, t‐Tau, p‐Tau, t‐Tau/Aβ‐42 ratio, and p‐Tau/Aβ‐42 ratio biomarker analysis. Obtained data was processed and analyzed through the software SPSS 22.0.

Result

Comparison between control patients and patients with AD, as defined by clinical diagnosis, did not show significant differences regarding to Aβ‐42 expression in CSF (U=91,000; p=0,067), (AD=1119,0360, SD=708,98952 vs CTRL=775,2623 SD=341,67835). However, there was a significant difference between groups concerning t‐Tau protein, (U=198,500; p=0,028), p‐Tau (U=250,00, p=0,001) and p‐Tau/Aβ‐42 ratio (U=238,00; p=0,005). In terms of cognitive variables, all showed significant differences between groups: MMSE (U=46,500, p=0,001), SVF (U=39,000; p<0,001), short term memory (U=27,000, p<0,001), recognition (U=72,500,p=0,014), as well as functionality (U=258,500, p<0,001). There was no difference regarding the age (U= 201,500; p=0,109) and formal education (U=201,500, p=0,109). As for the AD groups with positive and negative biomarkers, there was no significant difference in cognitive variables, age, formal education, and functionality.

Conclusion

AD group with negative biomarkers non differ in terms of cognition. Comparing the control and AD groups, there were differences in functionality, cognition, and biomarkers. However, comparing AD groups in terms of biomarkers, there was no difference in functionality performance, short‐term memory, fluency and general cognition. Therefore, the biomarkers do not indicate significant cognitive differences in the group of patients with dementia.
Low‐dielectric constant and viscosity tetrafunctional bio‐based epoxy resin containing cyclic siloxane blocks
Authors: Zhang Pengbo , Yao Tongjie , Xue Kangle , Meng Xianbin , Zhang Junying , Liu Li
Published: February 2022

Bio‐based epoxy resins with low‐dielectric constant, low viscosity and excellent mechanical properties have great significance for the future of advanced electronic and microelectronic industries. Cyclosiloxane segment possesses low polarity, high‐dissociation energy, and elevated molecular volume, thereby making it useful for the synthesis of materials with low dielectric constant and viscosity. Herein, a tetrafunctional eugenol‐based epoxy resin (DEP) based on a cyclosiloxane structure was designed and prepared through a hydrosilylation reaction. Allyl glycidyl ether (AGE) was selected as a reference compound and generated a silylation epoxy resin (AGDEP). The viscosity of these silicone‐containing tetrafunctional epoxy monomers (< 0.315 Pa·s) was significantly lower than that of the conventional oil‐based epoxy resin (14.320 Pa·s). After curing with methyl hexahydrophthalic anhydride (MHHPA), the dielectric constant of DEP‐MHHPA was as low as 2.8 (10 MHz), which was superior to that of EP‐MHHPA. Notably, the glass transition temperature (Tg) of DEP‐MHHPA was as high as 100.3°C. The tensile strength and elongation at break of DEP‐MHHPA were estimated to be 66.1 MPa and 6.0%, respectively. Multifunctional eugenol‐based epoxy monomers with low‐dielectric constant and viscosity provide an efficient guideline for building epoxy‐based materials to better design future‐oriented engineering materials.
Persistent phosphors for luminous paints: A review
Authors: Thejo Kalyani N. , Jain Abhilasha , Dhoble S. J.
Published: February 2022

The article briefly reports the fundamental scientific principles and landmarks in the field of luminescence and further enlightens the importance of persistent phosphor that is now widely used in luminous paints. Its main focus is on phosphorescence that makes use of lanthanides that have gained paramount importance in various cross‐sections of luminescent applications. Both inorganic and organic afterglow materials, synthesis and characterization along with skilled researchers' essential updates on emerging trends and efforts are elucidated at length. It exclusively reviews the red/green/blue organic/inorganic/hybrid phosphorescent materials and the latest advances in the development of novel long afterglow materials that can accelerate the green technology in the world of luminescence.
Longitudinal assessment of magnetization transfer ratio, brain volume, and cognitive functions in diffuse axonal injury
Authors: Macruz Fabiola Bezerra de Carvalho , Feltrin Fabrício Stewan , Zaninotto Ana , Guirado Vinícius Monteiro de Paula , Otaduy Maria Concepcion Garcia , Tsunemi Miriam Harumi , Nucci Mariana Penteado , Rimkus Carolina , Andrade Celi Santos , Leite Claudia da Costa
Published: February 2022

Background

Diffuse axonal injury (DAI) is a frequent mechanism of traumatic brain injury (TBI) that triggers a sequence of parenchymal changes that progresses from focal axonal shear injuries up to inflammatory response and delayed axonal disconnection.

Objective

The main purpose of this study is to evaluate changes in the axonal/myelinic content and the brain volume up to 12 months after TBI and to correlate these changes with neuropsychological results.

Methods

Patients with DAI (n = 25) were scanned at three time points after trauma (2, 6, and 12 months), and the total brain volume (TBV), gray matter volume, and white matter volume (WMV) were calculated in each time point. The magnetization transfer ratio (MTR) for the total brain (TB MTR), gray matter (GM MTR), and white matter (WM MTR) was also quantified. In addition, Hopkins verbal learning test (HVLT), Trail Making Test (TMT), and Rey–Osterrieth Complex Figure test were performed at 6 and 12 months after the trauma.

Results

There was a significant reduction in the mean TBV, WMV, TB MTR, GM MTR, and WM MTR between time points 1 and 3 (p < .05). There was also a significant difference in HVLT‐immediate, TMT‐A, and TMT‐B scores between time points 2 and 3. The MTR decline correlated more with the cognitive dysfunction than the volume reduction.

Conclusion

A progressive axonal/myelinic rarefaction and volume loss were characterized, especially in the white matter (WM) up to 1 year after the trauma. Despite that, specific neuropsychological tests revealed that patients’ episodic verbal memory, attention, and executive function improved during the study. The current findings may be valuable in developing long‐term TBI rehabilitation management programs.
Structural Characterization and Tumor Microvascular Inhibition Activity of Total Polysaccharide from Trametes sanguinea Lloyd
Authors: Yan MengXia , Zhang MengTing , Zhu ZhiHui , Zhang JianFen , Cheng GuiLin , Lin NengMing , Zhao HuaJun , Yang Bo
Published: February 2022

Trametes sanguinea Lloyd total polysaccharide (TsLTP), was obtained by water extraction and ethanol precipitation from T. sanguinea. The structural characterization of TsLTP was elucidated mutually by TsL1 and TsL2, whose mass ratio is 1: 4. TsL1 is mainly composed of mannose, glucose, galactose, and fucose, and consist of T‐Linked‐Fucp, T‐Linked‐Manp, T‐Linked‐Galp, 1,4‐Linked‐Manp, 1,4‐Linked‐Glcp, 1,6‐Linked‐Manp, 1,6‐Linked‐Galp, 1,3,4‐Linked‐Glcp, 1,4,6‐Linked‐Glcp and 1,3,6‐Linked‐Glcp, with a molar ratio of 2.1: 1.7: 1.4: 1.0: 3.6: 2.0: 8.6: 1.3: 2.2: 1.2, while TsL2 mainly comprise of glucose and consist of T‐Linked‐Glcp, 1,3‐Linked‐Glcp, 1,4‐Linked‐Glcp and 1,4,6‐Linked‐Glcp, with a molar ratio of 1.0: 2.1: 7.6: 1.4. TsLTP exhibited strong inhibitory effects on the migration, invasion, and tube formation of human umbilical vein endothelial cells (iHUVECs) and chick embryo chorioallantoic membrane (CAM) angiogenesis, whereas no inhibitory activity on human TNBC cell lines. Taken together, our study suggests that TsLTP possesses a significant inhibition of tumor microvascular activity both in vitro and in vivo. The study of TsLTP with novel monosaccharide composition and tumor microvascular inhibitory activity might be a beneficial attempt for application of polysaccharide from the genus Trametes in tumor therapy.
Gas flow Stimulated Hydrodynamics for Preparation and Application of Platinized Titanium Hollow Fibre Electrodes
Authors: Jong Ronald P. H. , Mul Guido
Published: February 2022

In this study, Pt was electrodeposited on the surface of Ti hollow fibres from PtCl62− solution at fixed potential and at variable gas flow rate. Partial Pt coverage of Ti was obtained at flow rates≤5 mL⋅min−1, while a more‐even geometrical distribution and linearly increasing Electrochemical Surface Area (ECSA) of Pt was obtained for flow rates of >5 and <20 mL⋅min−1. Above 20 mL⋅min−1, the morphology did not significantly change, and only a limited increase in ECSA of Pt (PtECSA) was observed. Second, the performance of the Pt functionalized Ti‐HFEs was evaluated at fixed potential in i) liquid phase oxidation of FeII to FeIII, and ii) the hydrogen (gas) evolution reaction (HER). Generally, for the oxidation of Fe(CN)64−, a linear increase in current from 3 to ≈9 mA was found as a function of increasing gas flow rate. For the HER, a gas evolving reaction, initially (in the range of 0–10 mL⋅min−1) a much larger enhancement in current (from ≈‐10 to −35 mA) was observed than consecutively at higher flow rates. The effect of gas flow rate on Pt deposition, and utilization of platinized Ti HFEs, is explained on the basis of increasing fractional participation of relatively small pores at high flow rates, and generally an increasing mass transfer coefficient (kM) associated with localized mixing of the electrolyte near the electrode/electrolyte interface. The kM is roughly in the same order of magnitude as obtained in experiments using rotating disc electrodes.
Differential impact of TGFβ/SMAD signaling activity elicited by Activin A and Nodal on endoderm differentiation of epiblast stem cells
Authors: Knowles Hilary , Santucci Nicole , Studdert Joshua , Goh Hwee Ngee , Kaufman‐Francis Keren , Salehin Nazmus , Tam Patrick P. L. , Osteil Pierre
Published: February 2022

Allocation of cells to an endodermal fate in the gastrulating embryo is driven by Nodal signaling and consequent activation of TGFβ pathway. In vitro methodologies striving to recapitulate the process of endoderm differentiation, however, use TGFβ family member Activin in place of Nodal. This is despite Activin not known to have an in vivo role in endoderm differentiation. In this study, five epiblast stem cell lines were subjected to directed differentiation using both Activin A and Nodal to induce endodermal fate. A reporter line harboring endoderm markers FoxA2 and Sox17 was further analyzed for TGFβ pathway activation and WNT response. We demonstrated that Activin A‐treated cells remain more primitive streak‐like when compared to Nodal‐treated cells that have a molecular profile suggestive of more advanced differentiation. Activin A elicited a robust TGFβ/SMAD activity, enhanced WNT signaling activity and promoted the generation of DE precursors. Nodal treatment resulted in lower TGFβ/SMAD activity, and a weaker, sustained WNT response, and ultimately failed to upregulate endoderm markers. This is despite signaling response resembling more closely the activity seen in vivo. These findings emphasize the importance of understanding the downstream activities of Activin A and Nodal signaling in directing in vitro endoderm differentiation of primed‐state epiblast stem cells.
Operation of a Solid Oxide Fuel Cell Reactor with Multiple Stacks in a Pressured System with Fuel Gas Recirculation
Authors: Tomberg Marius , Heddrich Marc Philipp , Metten Matthias , Ansar Syed Asif , Friedrich Kaspar Andreas
Published: February 2022

Large‐scale modular solid oxide fuel cell (SOFC) reactors composed of multiple stacks are regarded as an efficient form of power generation and important for the global energy transition. However, such an arrangement leads to several operational challenges, and methods are required for handling such challenges and understanding their sources. Hence, a test rig for the examination of a 30 kW SOFC reactor with multiple stacks, for operation near real system conditions, is built. The test rig, which allows operation at elevated pressure, is equipped with a high‐temperature blower that recirculates the fuel gas at SOFC reactor temperature. In a measurement campaign, fuel gas, reactant conversion, and pressure are varied in stationary and transient experiments. The experimental results showed that the operating conditions of the individual stacks of large SOFC reactors vary largely due to flow distribution and heat losses. Methods for the investigation of these critical characteristic parameters are derived from the experimental results. Furthermore, the impact of pressurization and fuel gas recirculation on the SOFC reactor is analyzed. This publication shows the need to understand the behavior of large SOFC reactors with multiple stacks to increase the performance and robustness of complete process systems.
Hall effects on MHD chemically reacting flow of second grade fluid past a vertical porous plate
Authors: Ahammad N. Ameer , Krishna M. Veera , Aljohani A. F.
Published: February 2022

The scrutiny of the consequences of radiation‐absorption, chemical reaction impacts on unsteady magnetohydrodynamics heat and mass transportation laminar flow of a gelatinous, electrical conducting by the heat generation or absorption second grade fluid embedded past a half‐unlimited porous surface within a gyratory structure taking Hall effects into account have been discussed. The plate is assumed to as in the motion by the invariable velocity contained by the direction of fluid movement. A uniform magnetic field performed at perpendicular to the porous plate; this is engrossing the fluid with the suction velocity changing with definite instants of time. The corresponding dimensionless governing equations of current configuration are solved by making use of perturbation technique with reference to harmonic and nonharmonic idioms. The velocity, temperature, and concentration profiles are discussed and examined with references to various governing parameters in detail. The results are verified with the published work. The velocity components are increased with increasing permeability and Hall parameters. It is noticed that practical application of Hall effects is as, washing machine dial to select the type of washing moves very smoothly. This problem has also applications in biomedical and aerospace engineering.
PBMC CDC42 reveals the disease activity and treatment efficacy of TNF inhibitor in patients with ankylosing spondylitis
Authors: Zhang Qian , Jin Du , Mou Xiaoyue , Ye Hengli
Published: February 2022

Objective

Cell division cycle 42 (CDC42) regulates the polarization of M2 macrophage and maintains the T cell homeostasis, to participate in multiple autoimmune diseases, while its clinical involvement in ankylosing spondylitis (AS) remains unclear. Hence, the current study aimed to investigate the correlation of CDC42 with clinical characteristics and treatment outcome in AS patients receiving tumor necrosis factor (TNF) inhibitor therapy.

Methods

Peripheral blood mononuclear cell (PBMC) CDC42 expression was detected at baseline, week (W) 4, W8, and W12 after TNF inhibitor treatment in 91 AS patients and in 50 HCs after enrollment. Furthermore, serum TNF‐α, interferon‐γ (IFN‐γ), interleukin‐10 (IL‐10), and interleukin‐17A (IL‐17A) from AS patients were detected at baseline.

Results

Blood CDC42 was lower in AS patients compared with HCs (p < 0.001). Additionally, blood CDC42 was negatively linked with CRP (r = −0.349, p = 0.001), BASDAI score (r = −0.243, p = 0.020), and ASDASCRP score (r = −0.238, p = 0.023) in AS patients; however, blood CDC42 was not correlated with other clinical characteristics. Besides, CDC42 was negatively correlated with TNF‐α (r = −0.237, p = 0.024) and IL‐17A (r = −0.339, p = 0.001) but not with IFN‐γ (p = 0.083) or IL‐10 (p = 0.280). Moreover, blood CDC42 was elevated after TNF inhibitor treatment (p < 0.001). Meanwhile, blood CDC42 was not varied at baseline and W4 between response patients and non‐response patients, while it was higher at W8 (p = 0.019) and W12 (p = 0.002) in response patients than in non‐response patients after treatment.

Conclusion

Blood CDC42 deficiency links with elevated pro‐inflammatory cytokines, disease activity and unsatisfying response to TNF inhibitor in AS patients.
Marine phytoplankton resilience may moderate oligotrophic ecosystem responses and biogeochemical feedbacks to climate change
Authors: Martiny Adam C. , Hagstrom George I. , DeVries Tim , Letscher Robert T. , Britten Gregory L. , Garcia Catherine A. , Galbraith Eric , Karl David , Levin Simon A. , Lomas Michael W. , Moreno Allison R. , Talmy David , Wang Weilei , Matsumoto Katsumi
Published: February 2022

Are the oceans turning into deserts? Rising temperature, increasing surface stratification, and decreasing vertical inputs of nutrients are expected to cause an expansion of warm, nutrient deplete ecosystems. Such an expansion is predicted to negatively affect a trio of key ocean biogeochemical features: phytoplankton biomass, primary productivity, and carbon export. However, phytoplankton communities are complex adaptive systems with immense diversity that could render them at least partially resilient to global changes. This can be illustrated by the biology of the Prochlorococcus “collective.” Adaptations to counter stress, use of alternative nutrient sources, and frugal resource allocation can allow Prochlorococcus to buffer climate‐driven changes in nutrient availability. In contrast, cell physiology is more sensitive to temperature changes. Here, we argue that biogeochemical models need to consider the adaptive potential of diverse phytoplankton communities. However, a full understanding of phytoplankton resilience to future ocean changes is hampered by a lack of global biogeographic observations to test theories. We propose that the resilience may in fact be greater in oligotrophic waters than currently considered with implications for future predictions of phytoplankton biomass, primary productivity, and carbon export.