bluuebunny/crossref_metadata_2025_split huggingface dataset:
The combination of acetylcholinesterase inhibitor therapy and high‐frequency repetitive transcranial magnetic stimulation in Alzheimer’s disease: A preliminary fMRI study
Authors: Cui Dong , Jin Jingna , Wang He , Liu Zhipeng , Yin Tao 
Published: February 2022

AbstractBackgroundBasal forebrain (BF) cholinergic dysfunction is one of the characteristics in Alzheimer’s disease (AD). Acetylcholinesterase inhibitors (AChEI) are approved drus currently used for the clinical treatment of AD. However, drug therapy has considerable side effects, and not everyone can benefit from it. Previous studies have shown that repetitive transcranial magnetic stimulation (rTMS) can improve cognitive function in patients with AD. Therefore, we aimed to determine the effect of cholinergic treatment on BF functional brain networks using functional connectivity (FC) analysis, and investigate whether donepezil therapy combined with rTMS is superior to monotherapy of AD.MethodThirty AD patients received ten sessions of 10Hz high frequency rTMS (HF‐rTMS) at 110% of the motor threshold on the left dorsolateral prefrontal cortex (DLPFC) and the left lateral parietal cortex (combination therapy group, n=15) or sham stimulation (drug treatment group, n=15), added to their donepezil treatment (5mg/d), in a randomized double‐blind design. Fifteen untreated and age, gender and years of education matched AD patients served as control group. The resting‐state FC of BF was calculated using a seed‐based approach. Spearman correlation with false discovery rate (FDR) correction was used to investigate the relationship between clinical and cognitive tests scores and FC values.ResultCompared to control group, the combination therapy group showed BF seed‐based FC enhancement in the bilateral posterior cingulate cortex (PCC), superior parietal lobule, left hippocampus, precuneus, and cerebellum. Drug treatment patients showed increased BF‐related FC in the bilateral PCC, and left hippocampus, and cerebellum. In addition, combination therapy group patients had significantly higher BF seed‐based FC in the left PCC and precuneus than drug treatment patients. Moreover, these brain regions are mainly concentrated in the default mode network (DMN).ConclusionOur results indicate that the levels of functional connectivity between the BF and the DMN is significantly higher in the combination therapy group than that in the other groups, and which is positively correlated with improvements in MMSE and ADL. HF‐rTMS over the left DLPFC and the left lateral parietal cortex is an add‐on strategy of clinical significance in combination with donepezil in patients with AD.
Within‐ and across‐network relationships between cortical atrophy and hypometabolism across A/T/N subgroups of the Alzheimer's disease continuum
Authors: Stocks Jane , Popuri Karteek , Rosen Howard J. , Beg Mirza Faisal , Wang Lei 
Published: February 2022

AbstractBackgroundNeurodegeneration caused by pathological protein aggregation in Alzheimer’s disease (AD) is reflected in cortical atrophy and glucose hypometabolism, measured with structural MRI and FDG‐PET, but how these disease processes relate to each other within and across brain networks remains unclear. We examine multimodal neuroimaging relationships within and between multiple large‐scale brain networks among CSF‐defined (i.e., amyloid, total tau, and p‐tau) “A/T/N” subgroups of AD.MethodAlzheimer’s Disease Neuroimaging Initiative subjects with CSF analysis, MRI and FDG‐PET: AD‐Continuum (A+(T or N ‐/+), N = 559), Suspected Non‐AD Pathologic Change (SNAP) (A‐(T or N+), N = 149), Normal (A‐T‐N‐, N = 179). T1‐MPRAGE scans underwent FreeSurfer processing to estimate cortical thickness, normalized 18FDG‐PET images were co‐registered and uptake values were projected onto corresponding cortical surface. Using a well‐validated atlas, MRI and FDG‐PET images were parcellated into 360 cortical “patches” corresponding to 12 cortical networks. Partial Pearson correlations were computed between the 360 patches of cortical thickness and FDG metabolism and displayed visually as heatmaps, organized by network. Bonferroni correction was used to account for multiple comparisons.ResultLimited significant correlations were seen in Normal subjects (Figure 1). Among SNAP subjects, positive within‐network correlations between atrophy and hypometabolism were found within the dorsal attention, frontoparietal and default‐mode networks (Figure 2). Across‐network relationships were also present with hypometabolism in the dorsal attention and frontoparietal networks associated with widespread cortical atrophy. In AD‐Continuum subjects, positive within‐network correlations between cortical atrophy and glucose hypometabolism were most frequent within the dorsal attention, default‐mode and posterior multimodal networks (Figure 3). Across‐network relationships were frequent with atrophy within the dorsal attention and default‐mode networks associated with widespread hypometabolism and hypometabolism within the dorsal attention, frontoparietal and default‐mode networks associated with widespread atrophy.ConclusionThese findings suggest that, in both SNAP and AD‐Continuum subjects, local and distant relationships between cortical atrophy and hypometabolism are common, especially within regions known to be impacted by AD neuropathology (e.g., frontoparietal and default‐mode networks). SNAP subjects show fewer across‐network correlations as compared to AD‐Continuum, supporting the conclusion that tau aggregation drives local neurodegeneration while the relationships between amyloid and neurodegeneration are less region‐specific.
Associations between cognition, Aβ, and tau in adults with Down syndrome
Authors: Tudorascu Dana L. , HartleyZammit Sigan L.Matthew D. , Cody Karly Alex , Laymon Charles M. , Minhas Davneet S. , Zaman Shahid , Ances Beau M. , Mathis Chester A. , Klunk William E. , Johnson Sterling C. , Handen Benjamin L. , Christian Bradley T. , Cohen Ann D. 
Published: February 2022

AbstractBackgroundAdults with Down syndrome (DS) are widely affected by AD pathology by their 30’s and have a 70‐80% chance of clinical dementia by their 60’s. The aim of the present study was to explore the relationship between cognitive decline and tau pathology using a regression model to explore the associations between longitudinal rates of cognition and the cross‐sectional tau burden in adults with DS.MethodNinety‐two participants (age=39.19±8.44 at time of tau scan) with DS with multiple cognitive assessments over a period of 9 years, PiB scans over a period of 8 years, and one [18F]AV‐1451 scan were analyzed. Cognitive assessments included tests of overall function (DSMSE), memory (cued recall), executive function (Stroop), and motor function (Purdue pegboard). FreeSurfer (v5.3.0) was used for the definition of ROIs. A two‐stage analysis was performed for cognition and AV‐1451 correlations or PiB and AV‐1451 correlations: 1) a linear mixed model was applied to estimate the rates of change for cognitive outcomes or PiB over time and 2) the cognitive or PiB estimated rates from the trajectories were used as predictors of interest in a correlation analysis with AV‐1451 for each Braak‐associated (1‐6) region as the outcome.ResultStatistically significant associations were found between AV‐1451 retention in all Braak regions and cognitive assessments at alpha=0.05 , including cued recall, DSMSE, and the Purdue pegboard task, but not for the Stroop test (Table 1). Statistically significant associations were also found in Braak regions 3‐6 at alpha=0.05 between longitudinal PiB estimated amyloid trajectories and cross‐sectional AV‐1451 retention.ConclusionFor this DS population, we found inverse associations between rates of neuropsychological decline and higher tau pathology. In particular, decline in global cognition, verbal memory and motor function were all associated with higher tau pathology, while executive function was not. Further, longitudinal analyses demonstrated an association between cross‐sectional and accumulating amyloid pathology with increased tau pathology in regions associated with higher Braak stages.
Associations between misinformation around COVID‐19 pandemic, severity of social isolation, and cognitive impairment
Authors: Marin Anna , Vives‐Rodriguez Ana , DeCaro Renee , Schiloski Kylie A , Hajos Gabor P , Di Crosta Adolfo , Ceccato Irene , La Malva Pasquale , Lahdo Naheer C , Donnelly Kaleigh , Dong Jiali , Kasha Sabrina , Rooney Colleen E , Dayaw Judith Nicole Tejada , Marton Gabrielle , Wack Audrey , Hanger Vanessa A , Di Domenico Alberto , Turk Katherine W , Palumbo Rocco , Budson Andrew 
Published: February 2022

AbstractBackgroundIn the past year, new research has focused on the degree of misinformation regarding the COVID‐19 pandemic in younger and older adults. However, no study has assessed how social isolation and cognitive status influence misinformation regarding the COVID‐19 pandemic. For this reason, we sought to investigate the differences in misinformation on the current pandemic in older individuals with and without cognitive impairment and social isolation in Boston, MA (United States) and Chieti (Italy).MethodData has been obtained from 49 subjects from the Boston cohort and 138 from the Italian cohort. Both healthy older adults and individuals diagnosed with Mild Cognitive Impairment (MCI) or Alzheimer’s Disease (AD) Dementia were included. Cognitive status was assessed with a telephone administered neuropsychological battery and blind MoCA. Social isolation was evaluated with the Lubben social isolation scale and misinformation with a COVID‐19 Misinformation Questionnaire. Associations between these variables were assessed using Pearson correlation and binary logistic regression.Result35 participants in our sample (26%) met the cutoff for social isolation. 95 subjects (70%) were cognitively impaired. Subjects that were at a higher risk of being socially isolated were more cognitively impaired (r=0.43, N=181, p<.001). Also, they were less likely to know the correct age group that is most affected by the pandemic (b =0.06; p <0.05) and were less likely to feel informed about protective measures that should be taken to avoid contracting COVID‐19 (r=0.24, N=181, p<.001). Subjects that were more cognitively impaired were more likely to think that the COVID‐19 was a bioweapon developed by a government or terrorist organization (b =0.15; p <.001) and were more likely to incorrectly think that a person could not be COVID‐19 positive and be asymptomatic (b =0.17; p <.01). More analysis will be completed once recruitment is completed.ConclusionSocial isolation and cognitive impairment were associated with a higher degree of misinformation about COVID‐19 and less information about protective measures against infection, making patients with these characteristics a vulnerable population during the current pandemic.
Understanding the impact of COVID‐19 pandemic on patients with Alzheimer’s disease and caregivers using online narratives on social media
Authors: Monfared Amir Abbas Tahami , Stern Yaakov , Doogan Stephen , Bray Margaret , Zhang Quanwu 
Published: February 2022

AbstractBackgroundThe Covid‐19 pandemic has disproportionately impacted individuals with pre‐existing health conditions. This study aims to describe the challenges of people with Alzheimer’s disease (AD) and their caregivers experienced during the pandemic.MethodWe used the RLytics NLP (Natural Language Processing) platform to analyze key challenges and issues that were shared online over 47 social media sites by patients living with AD and caregivers during the COVID‐19 pandemic between January 2020 and January 2021.ResultA total of 3,422 narratives were analyzed and reported in aggregate categories, including extensive descriptions on the worsening of AD, difficulties in understanding and maintaining rules of masking and social distancing, limited opportunities of social interactions, reduced caregiver availability, and emotional disturbance or exacerbation with fear, anxiety, and loneliness (Table). Disease worsening manifested with or without COVID‐19 diagnosis, leading to increased reliance and need for caregiver assistance and declining patient wellbeing. The patient challenges were compounded by increased caregiver burden, expressed through the social media on disruptions to Work‐from‐Home routines and the need for additional caregiver support to sustain household income. The caregiver narratives revealed a range of challenges, including common issues of getting access to COVID‐19 vaccines and unique issues of having to reminding or assisting patients with handwashing, social distancing, or staying at home. Patient disease aggravation resulting from restrictive caregiver access to long term care facilities was frequently communicated online by the caregivers, highlighting increased caregiver emotional stress that led to anger, frustration, crying, loneliness, depression and emotional fatigue.ConclusionThis social media study using NLP uncovers a broad range of challenges experienced by patients with AD and the caregivers during the COVID‐19 pandemic. They appear to have suffered unique health, cognitive, social, emotional, interpersonal, and daily living burden, resulting in worsening of disease and declining wellbeing. The untoward consequences may well likely surpass the pandemic, leading to prolonged deleterious impact in patient and caregiver personal lives and deepened public health crisis with AD.
A day in the life of caregivers to older adults with and without dementia: Comparisons of care time and emotional health
Authors: Freedman Vicki A. , Patterson Sarah E. , Cornman Jennifer C. , Wolff Jennifer L. 
Published: February 2022

AbstractIntroductionHow care‐related time and emotional health over the day differ for those assisting older adults with and without dementia is unclear.MethodsUsing 2134 time diaries from the National Study of Caregiving, we compared emotional health and care time for caregivers of older adults with and without dementia.ResultsCaregivers to older adults with dementia experienced worse (higher scores) on a composite measure of negative emotional health (4.2 vs 3.3; P < .05) and provided more physical/medical care (33.7 vs 16.2 minutes; P < .05) and less transportation assistance (12.6 vs 24.8 minutes; P < .05) than other caregivers. In models, providing physical/medical care was associated with worse emotional health (β = 0.15; P < .01) and socializing with the care recipient was associated with worse emotional health when the recipient had dementia (β = 0.28; P < .01).DiscussionFindings highlight the opportunity for targeted interventions to address the emotional consequences of different types of care time in the context of dementia.
A new definition of brain reserve
Authors: Hachinski Vladimir , Avan Abolfazl 
Published: February 2022

AbstractBrain reserve definitions foster debate and disagreements. A consensus definition of brain reserve would fill gaps in converging ongoing research and action plans to promote brain health. Different terms are used for the capacity to adapt to life hardships and cognitive and social compliance and to neutralize or compensate for age‐related neurological degeneration to prevent impaired cognition. Brain reserve, resilience, cognitive reserve, and brain maintenance have been used usually in isolation, but at times interchangeably. However, the need remains for a simplified overarching definition of brain reserve. Brain health is a continuous development and exercise of the brain, and thus the brain reserve requires a definition encompassing this continuum. We propose for discussion a new definition of brain reserve that incorporates available definitions and emphasizes the dynamic and interactive nature of a healthy brain. Brain reserve is the lifelong, dynamic, interactive, accumulating capacity to resist physical, emotional, and/or social harms.
The role of nativity in heterogeneous dementia incidence in a large cohort of three Asian American groups and white older adults in California
Authors: Hayes‐Larson Eleanor , Fong Joseph , Mobley Taylor M. , Gilsanz Paola , Whitmer Rachel A. , Gee Gilbert C. , Brookmeyer Ron , Mayeda Elizabeth Rose 
Published: February 2022

AbstractIntroductionLiterature shows lower dementia incidence in Asian American groups versus whites, varying by Asian ethnicity. One hypothesized driver is nativity differences (eg, healthy immigrant effect).MethodsWe followed a cohort of 6243 Chinese, 4879 Filipino, 3256 Japanese, and 141,158 white Kaiser Permanente Northern California members for incident dementia (2002 to 2020), estimating age‐adjusted dementia incidence rates by ethnicity and nativity, and hazard ratios (HR) for nativity on dementia incidence using ethnicity‐stratified age‐ and sex‐adjusted Cox proportional hazards models.ResultsDementia incidence appeared higher in foreign‐ versus US‐born Filipinos (HR, 95% confidence interval: 1.39, 1.02 to 1.89); differences were small in Japanese (1.07, 0.88 to 1.30) and Chinese (1.07, 0.92 to 1.24). No nativity differences were observed among whites (1.00, 0.95 to 1.04).DiscussionNativity does not explain lower dementia incidence in Asian Americans versus whites, but may contribute to heterogeneity across Asian ethnicities. Future research should explore differential impacts of social and cardiometabolic factors.
Rhodium‐Catalyzed ON‐OFF Switchable Hydrogenation Using a Molecular Shuttle Based on a [2]Rotaxane with a Phosphine Ligand
Authors: Tang Yu‐Ping , Luo Yi‐Er , Xiang Jun‐Feng , He Yan‐Mei , Fan Qing‐Hua 
Published: February 2022

AbstractA novel pH‐responsive molecular shuttle based on a [2]rotaxane with a phosphine ligand has been designed and synthesized. In the rhodium‐catalyzed hydrogenation of α,β‐dehydroamino acid esters and aryl enamides, ON/OFF‐switchable catalysis was accomplished with high ON/OFF ratios by adjusting the movements of the rotaxane wheels located at the catalyst terminals with acid/base. Mechanistic studies using NMR spectroscopy and quasi in situ X‐ray photoelectron spectroscopy revealed that RhIII‐hydride species are possibly formed in a H2 atmosphere when the catalyst is in the OFF state. During the reaction, a heterolytic activation of dihydrogen occurs by the interlocked rotaxane dibenzylamine and RhI catalytic center acting as a frustrated Lewis pair. Subsequent homolytic splitting of dihydrogen with the newly formed RhI‐hydride species generates RhIII‐hydride species. These findings show that a substrate‐selective hydrogenation can be achieved by using the OFF‐state catalyst.
MOF Synthesis Prediction Enabled by Automatic Data Mining and Machine Learning**
Authors: Luo Yi , Bag Saientan , Zaremba Orysia , Cierpka Adrian , Andreo Jacopo , Wuttke Stefan , Friederich Pascal , Tsotsalas Manuel 
Published: February 2022

AbstractDespite rapid progress in the field of metal–organic frameworks (MOFs), the potential of using machine learning (ML) methods to predict MOF synthesis parameters is still untapped. Here, we show how ML can be used for rationalization and acceleration of the MOF discovery process by directly predicting the synthesis conditions of a MOF based on its crystal structure. Our approach is based on: i) establishing the first MOF synthesis database via automatic extraction of synthesis parameters from the literature, ii) training and optimizing ML models by employing the MOF database, and iii) predicting the synthesis conditions for new MOF structures. The ML models, even at an initial stage, exhibit a good prediction performance, outperforming human expert predictions, obtained through a synthesis survey. The automated synthesis prediction is available via a web‐tool on https://mof‐synthesis.aimat.science.
Identification of a novel colon adenocarcinoma cell targeting peptide using phage display library biopanning
Authors: Bakhshinejad Babak , Sadeghizadeh Majid 
Published: February 2022

AbstractPhage display is well recognized as a promising high‐throughput screening tool for the discovery of novel cancer‐targeting peptides. Here, we screened a phage display library of 7‐mer random peptides through in vitro biopanning to isolate peptide ligands binding to SW480 human colon adenocarcinoma cells. Three rounds of negative and positive selection caused a remarkable enrichment of colon cancer cell‐binding phage clones with a significant enhancement of phage recovery efficiency (about 157‐fold). A number of phage clones were picked out from the eluted phages of last selection round and sequenced. According to the results of cell binding assay and phage cell‐based ELISA, one of the isolated peptides denoted as CCBP1 (with the sequence HAMRAQP) was indicated to have the highest binding efficiency, selectivity, and specificity toward colon cancer cells with no significant binding to control cells. Peptide competitive inhibition assay revealed that binding of the phage‐displayed CCBP1 is competitively inhibited by the same free peptide, suggesting that CCBP1 specific binding to the target cell is independent of the phage context. Taken together, our findings provide support for the notion that CCBP1 binds specifically to colon cancer cells and might be a potential lead candidate for targeted delivery of imaging agents or therapeutic genes/drugs to colon tumors.
Signatures of malignant cells and novel therapeutic targets revealed by single‐cell sequencing in lung adenocarcinoma
Authors: Liang Jiaqi , Chen Zhencong , Huang Yiwei , Bi Guoshu , Bian Yunyi , Jin Xing , Zhang Huan , Sui Qihai , Zhan Cheng , Wang Qun 
Published: February 2022

AbstractBackgroundSingle‐cell transcriptomics has been used to investigate various tumors to elucidate the molecular distinction of all cell type compositions of a complex mix.AimsThis study aimed to investigate malignant‐cell‐specific genes to explore diagnostic and therapeutic biomarkers using single‐cell transcriptomic data of lung adenocarcinoma.Materials & Methods10X single‐cell RNA‐seq data of fourteen patients with lung adenocarcinoma were analyzed. Genes that expressed differentially and those with higher confidence to distinguish tumor cells from normal cells were picked out using the ROC curves. The LASSO regression method was used to select most markedly correlated genes to predict the malignancy of every single cell within a model. We also conducted further experiments to determine their roles in lung cancer in vitro.ResultsTwenty two thousand four hundred and ninety one tumor and 181 666 normal single cells were analyzed where 369 genes were found to be specifically expressed in single malignant cells. Seventy of them, encoding secreted or membrane‐bound proteins, showed involvement in cell‐to‐cell communications in tumor biology. KRT18 and the other six genes were identified as predictors to distinguish single malignant cells and were integrated to construct an accurate (96.1%) predicting model. Notably, IRX2, SPINK13, and CAPN8 outperformed the other four genes. Further experiments confirmed the upregulation of them in lung adenocarcinoma at both tissue and cell levels. Proliferative capacities of lung adenocarcinoma cells were attenuated by knocking‐down of either of them. However, targeting CAPN8, IRX2, or SPINK13 hardly exerted a cytotoxic effect on these cells.DiscussionApart from the current model, similar tools were still warranted using single‐cell RNA‐seq data of more types of tumors. The three genes identified as potential therapeutic targets in the present study still need to be validated in more in lung cancer.ConclusionOur model can aid the analyses of single‐cell sequencing data. CAPN8, IRX2, and SPINK13 may serve as novel targets of targeted and immune‐based therapies in lung adenocarcinoma.