bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single step capture and assessment of multiple plasma extracellular vesicle biomarkers in Alzheimer's disease detection
Authors: Lewis Jean M , Harris Dorathy-Ann , Kosmatka Janell , Mikrut Emily , Evenson Jack , Balcer Heath I , Dhani Harmeet , Hinestrosa Juan Pablo , Rissman Robert , Billings Paul R 
Published: November 2024

Background Blood tests for Alzheimer's disease (AD) that measure biomarkers related to neuropathology have demonstrated to be useful, minimally-invasive ways to identify patients for screening into clinical trials. While some AD biomarkers can be detected in plasma, greater sensitivity is needed to make plasma AD tests more effective. Extracellular vesicles (EVs) in plasma carry AD-related biomarkers from the brain and could offer a concentrated source of brain-related biomarkers, though the methodological complexities involved in isolating plasma EVs have hampered its validation for clinical use. Objective To explore the feasibility and effectiveness of developing blood tests for AD utilizing extracellular vesicle-bound protein biomarkers. Methods We developed a simplified method for isolating EVs directly from plasma using an alternating current electrokinetic (ACE) microchip. No sample pretreatment steps were needed. Protein biomarkers on the EVs were detected by adding fluorescent antibodies to the plasma samples before capture by the chip. This allowed measurement of EV biomarker levels directly on the chip. Results AD or non-AD control plasma was measured for ten different AD-related biomarkers. EV-associated NCAM1, pTau231, α-synuclein, and TDP-43 levels were able to distinguish a group of 10 AD, 10 mild cognitive impairment (MCI), and 10 non-AD subjects. pTau231 was different between AD and non-AD (p = 0.0300) and α-synuclein differentiated AD from MCI (p = 0.0148). Conclusions This study shows how ACE microfluidic chip technology can help differentiate AD and MCI patients from non-AD controls with clinical relevance. This work also highlights the important diagnostic role of plasma EV biomarkers in neurodegenerative disease.
A systematic review of lifestyle-based interventions for managing Alzheimer's disease: Insights from randomized controlled trials
Authors: Martínez-López Sara , Tabone Mariangela , Clemente-Velasco Sara , González-Soltero Maria del Rocío , Bailén María , de Lucas Beatriz , Bressa Carlo , Domínguez-Balmaseda Diego , Marín-Muñoz Juan , Antúnez Carmen , Gálvez Beatriz G , Larrosa Mar 
Published: November 2024

Background Alzheimer's disease (AD) presents a significant challenge in healthcare, prompting exploration into non-pharmacological interventions to complement traditional treatments. Objective This systematic review explores the efficacy of lifestyle-based interventions in managing AD. Methods A comprehensive literature search was conducted in PubMed, Web of Science, and Scopus between 2018 and 2023, selecting randomized controlled trials examining factors such as exercise, diet, stress, and cognitive training in AD patients. Results The review revealed physical exercise as the predominant non-pharmacological intervention, accompanied by dietary modifications, cognitive training, and therapies such as mindfulness and music. While exercise demonstrated improvements in quality of life, its cognitive benefits were limited. Modified diets, such as Atkins and ketogenic, displayed inconsistent effects on cognitive function but influenced other health-related parameters. Additionally, probiotic therapy and novel cognitive training technologies were explored. Conclusions Despite some interventions showing promise in enhancing cognitive function and slowing disease progression, uncertainties remain regarding the dose-response relationship, underlying mechanisms, and potential synergistic effects. Moreover, consideration of genetic and sex-based disparities is warranted. This synthesis underscores the need for further research to elucidate the nuances of non-pharmacological interventions in managing AD effectively. PROSPERO registration number CRD42023432823
Identification of key neutrophil extracellular trap genes in Alzheimer's disease
Authors: Pan Hengming , Wang Ge , Bi Zhichao , Lai Chao , Wang Min 
Published: November 2024

Background Alzheimer's disease (AD) is a neurodegenerative disorder that is associated with neuroinflammation. Neutrophil extracellular traps (NETs) are web-like structures that cause inflammation, but its involvement in AD pathogenesis is unclear. Objective This study aimed to identify key NETs related genes associated with AD. Methods A total of 180 samples from the GSE122063 and GSE36980 dataset were obtained from the GEO repository. The representative genes were obtained, and its diagnostic performance was evaluated by analyzing operating characteristic curves. Consensus clustering and principal component analysis were performed to cluster AD samples. Gene ontology, KEGG pathway enrichment, and protein interaction network were analyzed. Peripheral blood samples were collected from 5 AD patients and 5 healthy donors to determine the expression of representative proteins or genes using WB, ELISA, and RT-qPCR. Results A total of 297 differentially expressed genes (DEGs) were associated with AD, 18 NETs genes showed potential diagnostic value. NETs genes expression effectively distinguished AD patients into 2 subgroups. The AD1 cluster showed higher abundance of activated dendritic cells, monocytes, and neutrophils, the AD2 cluster showed higher levels of naive B cells, eosinophils, and activated NK cells. We randomly selected and measured the levels representative genes in AD patients. The levels of NETs and CCL2, TLR2 expressions were significantly increased, whereas the level of BDNF was significantly decreased in AD patients comparing with healthy controls. Conclusions This study identified key NET genes including BDNF, CCL2, and TLR2 to be associated with AD pathogenesis and classification.
Sleep disturbance impaired memory consolidation via lateralized disruption of metabolite in the thalamus and hippocampus: A cross-sectional proton magnetic resonance spectroscopy study
Authors: Fan Xiaowei , Mao Xin , Yu Ping , Han Ding , Chen Chuxin , Wang Hongqi , Zhang Xinyi , Liu Siyu , Chen Weijing , Chen Ziyan , Du Xiaoqiang , Jin Liangyun , Song Yizhi , Li Hui , Zhang Ning , Wu Yan , Chang Lirong , Wang Chunxue 
Published: November 2024

Background Memory consolidation in sleep-dependent individuals involves the circuitry connections of cortex, thalamus and hippocampus, regulating via neural metabolites. However, the disruption of metabolic pattern in thalamus and hippocampus remains unclear. Objective We aim to explore the disruptive effects of insomnia on the metabolites during memory consolidation, particularly the underlying neurometabolic mechanisms in comorbidity of failed memory consolidation. Methods This study integrates clinical research with animal experiment. In clinical research, 49 participants were divided into four groups: healthy controls (HC, n = 11), insomnia with normal cognition (IS, n = 14), mild cognitive impairment without insomnia (MCI, n = 10), and insomnia with mild cognitive impairment (IS-MCI, n = 14). Magnetic resonance spectroscopy (MRS) was used to evaluate the neural γ-aminobutyric acid (GABA) and glutamate–glutamine (Glx) in bilateral thalamus. In experimental studies, the rat model of sleep deprivation combined with amyloid-β (Aβ) injection was established, after behavior testing, the levels of Glx, choline (Cho) and N-acetyl aspartate (NAA) in the bilateral hippocampus were evaluated with MRS. Results The patients in the IS-MCI group exhibited significantly lower GABA level than IS, MCI and HC groups. Results from rat studies showed that sleep deprivation exacerbated asymmetric alterations in Aβ-induced bilateral hippocampal metabolite abnormalities, which correlated with cognition. These neuro-metabolite disruption accompanied with synaptic loss and activation of astrocytes. Conclusions The lateralized decrease in GABA levels of thalamus and NAA, Cho, and Glx levels of hippocampus under conditions of sleep disturbance with cognitive decline may provide evidence for the neural metabolic mechanisms underlying the disruption of memory consolidation.
Identification and cognitive function prediction of Alzheimer's disease based on multivariate pattern analysis of hippocampal volumes
Authors: Gao Ziwen , Zhu Wanqiu , Li Yuqing , Ye Wei , Chen Xiao , Zhou Shanshan , Li Xiaohu , Li Xiaoshu , Yu Yongqiang ,   the Alzheimer's Disease Neuroimaging Initiative
Published: November 2024

Background Alzheimer's disease (AD) is strongly associated with slowly progressive hippocampal atrophy. Elucidating the relationships between local morphometric changes and disease status for early diagnosis could be aided by machine learning algorithms trained on neuroimaging datasets. Objective This study intended to propose machine learning models for the accurate identification and cognitive function prediction across the AD severity spectrum based on structural magnetic resonance imaging (sMRI) of the bilateral hippocampi. Methods The high-resolution sMRI data of 120 AD dementia patients, 232 amnestic mild cognitive impairment (aMCI) patients, and 206 healthy controls (HCs) were included from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The classification capacity and cognitive predict ability of hippocampal volume was evaluated by multiple pattern analysis using the support vector machine (SVM) and relevance vector regression (RVR) application of the Pattern Recognition for Neuroimaging Toolbox, separately. For validation, the analyses were performed using a biomarker-based regrouping method and another independent local dataset. Results The SVM application produced a total accuracy of 94.17%, 80.85%, and 70.74% and area under receiver operating characteristic curves of 0.97, 0.87, and 0.72 between HC versus AD dementia, HC versus aMCI, and aMCI versus AD dementia classification, respectively. The RVR application significantly predicted the baseline and mean cognitive function at three years of follow-up. Qualitatively consistent results were obtained using different regrouping method and the local dataset. Conclusions The machine learning methods based on the bilateral hippocampi distinguished across the AD severity spectrum and predicted the baseline and the longitudinal cognitive function with greater accuracy.
Detection of molecular markers of ferroptosis in human Alzheimer's disease brains
Authors: Mayr Emily , Rotter Jonas , Kuhrt Heidrun , Winter Karsten , Stassart Ruth Martha , Streit Wolfgang J , Bechmann Ingo 
Published: November 2024

Background We have previously shown that droplet degeneration (DD) signifies the beginning of neuritic plaque formation during Alzheimer's disease (AD) pathogenesis. As microglia associated with neuritic plaques exhibited strong ferritin expression and Perl's iron staining showed iron in microglia, droplet spheres and neuritic plaque cores, we hypothesized that DD is a form of ferroptosis. Objective Detection of molecular markers of ferroptosis in AD brains. Methods Immunohistochemical detection of transferrin receptor (TfR) and ferritin as ferroptosis markers in prefrontal cortex of AD brains, investigation of spatial correlation of these with histopathological hallmarks of AD, visualization of ferroptotic marker genes by in situ hybridization, comparison of expression of ferroptosis genes with snRNAseq analyses and comparison of TfR and ferritin expression in different neurofibrillary tangle (NFT) stages. Results TfR was found on neurons that appeared to be degenerating and exhibited typical features of droplet degeneration. Co-localization with hyperphosphorylated tau (p-tau) was a rare event. TfR-positive neurons increased with higher NFT stages as did ferritin expression in microglia. mRNA of genes linked to ferroptosis was detected in pretangles and p-tau negative neurons, less in DD. snRNAseq analyses support a link between AD, ferroptosis and TfR as a ferroptosis marker. Conclusions Increased expression of TfR and ferritin in high NFT stages, demonstration of ferroptotic marker genes in Alzheimer's lesions, as well as snRNAseq analyses strengthen our hypothesis that DD represents ferroptosis. Because of the morphological similarity between TfR-positive structures and DD, TfR might be an early ferroptosis marker expressed transiently during AD pathogenesis.
Associations of neurocognitive and neuropsychiatric patterns with brain structural biomarkers and dementia risk: A latent class analysis
Authors: Zhang Yaping , Liao Yingqi , Yan Yifan , Kan Cheuk Ni , Zhou Yi , Fang Shenghao , Huang Jingkai , Hilal Saima , Chen Christopher LH , Xu Xin 
Published: November 2024

Background Neurocognitive and neuropsychiatric symptoms are essential clinical manifestations of age-related cognitive impairment, yet their patterns of co-existence remain unclear through the cognitive continuum. Objective To examine the associations of person-centered cluster-derived patterns, based on a comprehensive collection of domain-specific cognitive and neuropsychiatric assessments, with neuroimaging markers and dementia risk. Methods 641 participants were included in the analysis from memory clinics in Singapore. Latent class analysis was applied to define clusters of individuals with different clinical patterns. The associations between identified clinical groups with neuroimaging markers of cerebrovascular diseases and neurodegeneration were analyzed using logistic regression models. Cox proportional hazard models were applied for incident dementia. Results Three latent classes differing in neurocognitive and neuropsychiatric impairment were identified (Class 1 “memory impairment only”; Class 2 “global cognitive impairment”; Class 3 “global cognitive and neuropsychiatric impairment”). Compared with Class 1, Class 2 and 3 were associated with smaller brain volumes, moderate-to-severe cortical atrophy and medial temporal lobe atrophy, and the presence of all cerebrovascular lesions. Moreover, compared with Class 2, Class 3 had smaller brain volumes, moderate-to-severe cortical atrophy and presence of intracranial stenosis. Additionally, compared to Class 1, Class 2 (hazard ratio [HR] = 3.84, 95%CI 2.11–7.00), and Class 3 (HR = 6.92, 95%CI 2.84–16.83) showed an increased risk of incident dementia. Conclusions Participants characterized by multi-domain cognitive impairment and co-occurrence of cognitive and neuropsychiatric impairment showed the highest risk of incident dementia, which may be attributed to both neurodegenerative and cerebrovascular pathologies.
Operative versus non-operative treatment for non-displaced Lisfranc injuries: A two-center randomized clinical trial
Authors: Ponkilainen Ville , Mäenpää Heikki , Laine Heikki-Jussi , Partio Nikke , Väistö Olli , Jousmäki Janne , Mattila Ville M. , Haapasalo Heidi 
Published: November 2024

Background and aims: There is no consensus on which Lisfranc injuries can be treated non-operatively. The aim of the study was to compare non-operative treatment and open reduction and internal fixation (ORIF) in the treatment of non-displaced Lisfranc injuries. Materials and methods: This study was a multicenter randomized controlled trial (RCT) conducted at two hospitals in Finland between 19 March 2012, and 20 December 2022, with a target sample size of 60 patients. The primary outcome was Visual Analogue Scale Foot and Ankle (VAS-FA) at 2 years. The secondary outcomes included VAS-FA pain, function, and other complaints subscales and the American Orthopedic Foot & Ankle Society (AOFAS) Midfoot Scale. All outcomes were measured at 6 months, 1 and 2 years. Results: Altogether 27 patients with computed tomography (CT)-confirmed non-displaced Lisfranc injuries were enrolled in this trial resulting in an underpowered trial. In patients with non-displaced Lisfranc injuries, the mean VAS-FA overall score in the non-operative group was 96.1 [confidence interval (CI): 91.5–100] and 91.8 [86.9–96.7] in the ORIF group at 2 years with no statistically significant difference between the groups (mean between-group difference (MD) 4.3 [CI, −2.4 to 11], Cohen’s d = 0.706) in this underpowered RCT. Conclusion: There was no difference in VAS-FA between non-operative and ORIF in patients with non-displaced Lisfranc injuries, but the trial is underpowered to draw robust conclusions.
Deaf, deaf-blind, and hard of hearing needs and perceptions of community pharmacy services
Authors: Lim Timothy , Tsai Mel , Reyes Alecz , Kapanen Anita , D’Amato Felicia 
Published: November 2024

Background: Deaf, deaf-blind, and hard of hearing (D/DB/HOH) individuals face communication challenges affecting their health, which can lead to medication errors. Pharmacists can mitigate medication-related errors for D/DB/HOH individuals, but there is a lack of evidence-based best practices. This study explored the experiences of D/DB/HOH people at a community pharmacy and offered practical solutions to improve pharmaceutical care for D/DB/HOH individuals. Methods: A qualitative study consisting of 5 focus group discussions occurred. Focus groups were formed based on participants’ ability to use sign language, their hearing ability, and their age. Results: Nineteen participants completed the study (8 HOH adults, 2 HOH seniors, 1 deaf-blind adult, 4 deaf adults, and 4 deaf seniors). Communication barriers depended on one’s hearing ability but included factors such as assuming one can hear, environmental noises around the pharmacy, pharmacists not knowing American Sign Language, and assuming individuals are proficient at reading English. Focus group participants shared the potential and actual impacts that communication barriers can have on health. Strategies to improve communication between hearing pharmacists and D/DB/HOH individuals are discussed. Discussion: This is the first study in Canada exploring D/DB/HOH individuals’ experiences at community pharmacies. Focus groups were effective at revealing the similarities and differences in pharmacy experience between D/DB/HOH folks, calling attention to access barriers and their impacts on health, and highlighting ways to better meet the needs of D/DB/HOH individuals. Conclusion: Communication barriers result in a lack of understanding of one’s medications. Pharmacists should ask about communication preferences and aim to reduce communication barriers for those who are D/DB/HOH.
The interplay between dysregulated metabolites and signaling pathway alterations involved in osteoarthritis: a systematic review
Authors: Aziz Atiqah , Ganesan Nathan Kavitha , Kamarul Tunku , Mobasheri Ali , Sharifi Alimohammad 
Published: November 2024

Background: Osteoarthritis (OA) is a common degenerative joint disease that poses a significant global healthcare challenge due to its complexity and limited treatment options. Advances in metabolomics have provided insights into OA by identifying dysregulated metabolites and their connection to altered signaling pathways. However, a comprehensive understanding of these biomarkers in OA is still required. Objectives: This systematic review aims to identify metabolomics biomarkers associated with dysregulated signaling pathways in OA, using data from various biological samples, including in vitro models, animal studies, and human research. Design: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data sources and methods: Data were gathered from literature published between August 2017 and May 2024, using databases such as “PubMed,” “Scopus,” “Web of Science,” and “Google Scholar.” Studies were selected based on keywords like “metabolomics,” “osteoarthritis,” “amino acids,” “molecular markers,” “biomarkers,” “diagnostic markers,” “inflammatory cytokines,” “molecular signaling,” and “signal transduction.” The review focused on identifying key metabolites and their roles in OA-related pathways. Limitations include the potential exclusion of studies due to keyword selection and strict inclusion criteria. Results: The meta-analysis identified dysregulated metabolites and associated pathways, highlighting a distinct set of related metabolites consistently altered across the studies analyzed. The dysregulated metabolites, including amino acids, lipids, and carbohydrates, were found to play critical roles in inflammation, oxidative stress, and energy metabolism in OA. Metabolites such as alanine, lysine, and proline were frequently linked to pathways involved in inflammation, cartilage degradation, and apoptosis. Key pathways, including nuclear factor kappa B, mitogen-activated protein kinase, Wnt/β-catenin, and mammalian target of rapamycin, were associated with changes in metabolite levels, particularly in proinflammatory lipids and energy-related compounds. Conclusion: This review reveals a complex interplay between dysregulated metabolites and signaling pathways in OA, offering potential biomarkers and therapeutic targets. Further research is needed to explore the molecular mechanisms driving these changes and their implications for OA treatment.
Seasonal weight change during islamic holidays and effect of exercise on body weight and composition
Authors: Tutumlu Hazal , Cooper Jamie A. , Göktaş Zeynep 
Published: November 2024

Background There are several studies evaluating weight changes during the Christian and U.S. holiday season but data on the Muslim holiday season is limited. The purpose of this study was to assess the changes in body weight, body composition and blood pressure during Islamic holiday season among exercising and non-exercising participants. Methods The study was conducted with 63 eligible adults (30 men and 33 women; mean age 38.3 ± 13.9y, body mass index (BMI) of 24.4 ± 4.0 kg/m2). Participants who exercised for at least 150 min/week were included in the “exercisers” group (n = 30), while those performing <150 min/week were included in the “non-exercisers” group (n = 33). Subjects were evaluated before Ramadan and after Eid Al-Adha (total duration 18 weeks, early June-end of September, 2017). Data collected during each visit included height, weight, body composition, blood pressure, and physical activity level and food intake records. Results Non-exercisers gained 0.61 ± 0.20 kg weight (p = 0.005) while exercisers did not change weight (0.32 ± 0.31 kg, p = 0.336) over the holiday season. Similarly, non-exercisers had an increase in body fat % (0.90 ± 0.22%, p < 0.001) whereas exercisers showed a trend for fat loss (−0.55 ± 0.29%, p = 0.068). The changes between exerciser vs. non-exercisers was significantly different for body weight (p = 0.015), body fat percentage (p < 0.001), and systolic blood pressure (p = 0.03). Conclusions There was no change in weight, BMI or body fat % for exercisers during the Islamic holiday season. Meanwhile non-exercisers showed an increase in both body weight and body fat %, and that gain was different from exercisers. Our findings further validate that being physically active can prevent holiday season weight gain.