bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tear fluid reflects the altered protein expressions of Alzheimer's disease patients in proteins involved in protein repair and clearance system or the regulation of cytoskeleton
Authors: Kärkkäinen Virve , Hannonen Sanna , Rusanen Minna , Lehtola Juha-Matti , Saari Toni , Uusitalo Hannu , Leinonen Ville , Thiede Bernd , Kaarniranta Kai , Koivisto Anne M , Utheim Tor Paaske 
Published: November 2024

Background New biomarkers that improve diagnosis of Alzheimer's disease (AD) are warranted. Tear fluid (TF) containing variety of proteins that reflect pathophysiological changes of systemic diseases makes TF proteins potential biomarker candidates for AD. Objective We investigated the expression levels of TF proteins in persons with mild AD and cognitively healthy controls (CO) to find out if altered proteins may link to the AD pathophysiology. Methods We analyzed the data of the 53 study participants (34 COs, mean age 71 and Mini-Mental State Examination (MMSE) 28.9 ± 1.4 and 19 persons with AD, CDR 0.5–1, mean age 71 and MMSE 23.8 ± 2.8). All went through neurological status examination, cognitive tests, and ophthalmological examination. TF was collected using Schirmer strips. The TF protein content was evaluated via mass spectrometry-based proteomics and label-free quantification. Results Eleven proteins having a role either in protein repair and clearance system, or regulation of cytoskeleton, showed altered expression in AD group compared to CO group. Seven of them were significantly ( p ≤ 0.05) upregulated (Sti1, Twf1, Myl6, Otub1, Pls1 and Caza1) or, downregulated (HSP90) in AD group. Conclusions Altered expression of all these up- or downregulated proteins may be linked to AD pathophysiology. Thus, our results are encouraging for searching new biomarker candidates for AD. TF is potential biomarker candidate, because TF seems to reflect altered protein levels already in mild AD dementia.
The study of Alzheimer's disease risk diagnosis based on natural killer cell marker genes in the multi-omics data
Authors: Chen Xiaorong , Hu Fuyan , Chi Qingjia , Rao Congjun 
Published: November 2024

Background Alzheimer's disease (AD) is a common neurodegenerative disorder, currently lacking effective early diagnostic methods. However, natural killer (NK) cells may play a potential role in AD pathogenesis. Objective This study aims to identify AD-related feature genes from NK cell markers to construct a diagnostic model and explore their potential biological mechanisms in AD. Methods Single-cell RNA sequencing data was used to identify NK cell markers. A novel feature selection algorithm, adaptive dynamic graph convolutional network (ADGCN), was proposed to extract AD-related feature genes and construct a diagnostic model. Differential, correlation and enrichment analyses were performed to understand the biological mechanisms of these genes. Immune infiltration analysis compared the immune microenvironment between AD and controls. Two regulatory networks explored interactions between feature genes, transcription factors and microRNAs. The association between SNPs and feature genes' expression was examined through expression quantitative trait loci analysis. Differential CpG sites were identified to analyze their association with the NK cell markers' expression. Results We developed an optimal diagnostic model (ADGCN-XGBoost) with 17 feature genes, demonstrating high diagnostic effectiveness across datasets. These genes were primarily related to macromolecule biosynthesis, cytoplasmic translation biological processes and ribosome pathway, and potentially modulated immune infiltration of AD patients. We predicted 27 target miRNAs and 21 transcription factors influencing these genes. Multimodal analysis identified 57 significant SNP-gene associations and seven CpG-gene pairs. Conclusions This study proposed a novel feature selection algorithm and developed a diagnostic model based on 17 feature genes, providing new potential biomarkers for AD diagnosis.
Exacerbated mitochondrial dynamic abnormalities without evident tau pathology in rapidly progressive Alzheimer's disease
Authors: Xiyang Yanbin , Gao Ju , Ding Mao , Ren Xiaojia , Appleby Brian S , Leverenz James B , Miyagi Masaru , Pillai Jagan A , Perry George , Wang Xinglong 
Published: November 2024

Background Rapidly progressive Alzheimer's disease (rpAD) is a clinical subtype distinguished by its rapid cognitive decline and shorter disease duration. rpAD, like typical AD (tAD), is characterized by underlying neuropathology of amyloid plaques and neurofibrillary tangles. There is early evidence that the composition of amyloid plaques could vary between the rpAD and tAD. Differences in tau pathology between rpAD and tAD are also of interest. Additionally, mitochondrial dysfunction is a key early-stage change in tAD but has not yet been evaluated in rpAD. Objective To deepen our understanding of the underlying pathophysiological processes specific to rpAD, we explore potential changes in tau pathology and mitochondrial dysfunction in rpAD compared to tAD. Methods We performed immunohistochemical and immunoblot analyses of tau, phosphorylated tau, and key regulators of mitochondrial dynamics and bioenergetics in postmortem human temporal cortex tissues obtained from patients diagnosed with tAD or rpAD, and tissues from age-matched normal subjects. Results tAD was characterized by significant tau phosphorylation at the PHF1 epitope. Unexpectedly, rpAD showed milder PHF1 tau phosphorylation, similar to that of age-matched controls. Despite these differences in tau pathology, both tAD and rpAD exhibited a significant decrease in the key regulators of mitochondrial dynamics and bioenergetics compared to controls. However, the decline in mitochondrial dynamics regulators was more pronounced in rpAD. Conclusions These findings suggest divergent pathological processes between tAD and rpAD, specifically in terms of tau pathology and mitochondrial dynamic abnormalities, which underscore the necessity for different approaches to understand and potentially treat various AD subtypes.
Acceptability of bispectral Index monitoring in end-of-life care for dementia
Authors: Xu (须静媛) Jingyuan , Smaling Hanneke JA , Dahan Albert , Chan Justin , van der Steen Jenny T 
Published: November 2024

Background Assessing consciousness might benefit the care for people with Alzheimer's disease and other types of dementia at the end of life by indicating distressing symptoms and moments of awareness. This could guide symptom control and increase interaction with the person with dementia. Objective This study aims to investigate the acceptability of a biosignal measurement of consciousness, the Bispectral Index monitoring (BIS), for persons with dementia at the end of life. Methods Qualitative study using focus groups and interviews with demonstrations of BIS monitoring, with 17 individuals with dementia and 24 family caregivers. Qualitative content analysis was based on the theoretical framework of acceptability. Results People with dementia did not find BIS monitoring bothersome, yet acceptability varied across participants and situations. Family caregivers considered BIS acceptable for medical situations such as palliative sedation and pain assessment. Perceived effectiveness, ethicality, and usefulness considerations underpinned reasons and concerns around acceptability. Conclusions Potential end-users expressed diverse attitudes towards BIS monitoring in dementia end-of-life care. If BIS or similar technologies are to be implemented in the future, care must be taken to ensure that the device has sufficient added value, that the person with dementia and family are well informed, and that the technology does not replace human care. Future research should investigate its efficacy and feasibility in the situations that were deemed acceptable.
Exploring the role of miR-125b-5p as a pro-inflammatory factor in Alzheimer's disease pathology
Authors: Liu Wenjia , Chen Sophia , Rao Xin , Chen Xiaodong , Yu Liyang , Zhang Jiangtao , Chen Jiong , Cui Bohan 
Published: November 2024

Background Alzheimer's disease (AD) is a common neurodegenerative disease, where neuroinflammation significantly influences its pathophysiology by driving the disease's pathological cascade. As a pro-inflammatory regulator, miR-125b-5p contributes to AD progression, though its precise role and mechanisms remain unclear. Objective We aims to identify mRNAs significantly regulated by pro-inflammatory miR-125b-5p in AD and uncover key neuroinflammatory pathways. Methods Target mRNAs regulated by miR-125b-5p were predicted using online databases and analyzed with two mRNA datasets to identify differentially expressed mRNAs (DEmRNAs). Enrichment analysis was conducted to explore their biological functions and pathways. The significance of DEmRNAs expression in AD-related inflammatory pathways was verified by the Wilcoxon test, predictive accuracy was assessed via area under the curves (AUCs), and novel mRNAs were identified through positive control analysis. Results A total of 613 miR-125b-5p target mRNAs were identified, and 44 DEmRNAs were detected to be regulated by miR-125b-5p in two datasets. The 44 target DEmRNAs associated with AD include three key pathways: insulin signaling ( EXOC7, FLOT2, MKNK2), phosphatidylinositol signaling ( IP6K1, MTMR3), and phospholipase D signaling ( CYTH1, GAB2). Correlation analysis indicated strong correlations among 7 mRNAs, all showing significant differential expression, with AUCs above 0.5, confirming their predictive value. Three mRNAs ( EXOC7, IP6K1, CYTH1) were identified as novel AD-related genes. MiR-125b-5p binding sites in the 3′-UTRs of these 7 mRNAs suggest their potential roles in AD-related inflammation and signaling pathways. Conclusions This study investigates the pro-inflammatory miR-125b-5p's role in the pathological processes of AD, highlighting its regulation of key target mRNAs and critical pathways.
Coexistence of somatic and psychological symptoms of depression among community-dwelling older adults is associated with the incidence of dementia
Authors: Misu Yuka , Tsutsumimoto Kota , Kiuchi Yuto , Nishimoto Kazuhei , Ohata Tomoka , Shimada Hiroyuki 
Published: November 2024

Background Depression in old age is associated with the incidence of dementia. However, whether a combination of somatic and psychological symptoms influences the risk of dementia has not been fully investigated. Objective We aimed to determine the association between the combination of psychological and somatic symptoms of depression and the incidence of dementia. Methods This prospective cohort study included 2111 community-dwelling older adults (median age = 73 years, interquartile range = 68–78 years, 39.5% male). Participants were evaluated for 5 years from baseline to assess the incidence of dementia. Somatic symptoms were defined as the presence of one or more symptoms of fatigue, weight loss, sleep disturbances, and abnormal appetite. Psychological symptoms were assessed using the 15-item Geriatric Depression Scale. Participants were stratified into four groups based on the presence or absence of somatic and psychological symptoms. A Cox proportional hazards model was used to examine the associations with the incidence of dementia, adjusted for potential confounders. Results The hazard ratios for the incidence of dementia in the somatic (HR 1.42, 95% CI: 0.96–2.09) and psychological symptoms-only groups (HR 1.47, 95% CI: 0.83–2.59) were not significantly different; however, they were significantly higher in the coexistent group than in the normal group (HR 1.91, 95% CI: 1.24–2.94). Conclusions The coexistence of somatic and psychological symptoms of depression increases the risk of dementia. Therefore, interventions should consider both somatic and psychological symptoms to prevent or delay dementia.
Spatial differences in gene expression across the dorsal raphe nucleus in a model of early Alzheimer's disease
Authors: Kolling Louis J , Chimenti Michael S , Marcinkiewcz Catherine A 
Published: November 2024

Background Persons with Alzheimer's disease (AD) present with changes in mood, sleep, and arousal that may precede the clinical manifestation of cognitive decline. These early symptoms can be driven by changes in the serotonergic (5-HT) nuclei of the brainstem, particularly the dorsal raphe nucleus (DRN). It is unclear why all 5-HT neurons do not simultaneously develop AD pathology that progresses at the same rate. Objective We sought to identify any underlying genetic components associated with susceptibility or resistance of 5-HT neurons to AD pathology. Methods The Visium Spatial Gene Expression platform was used to identify transcriptomic changes across the DRN in a preclinical model of early AD, human tau-overexpressing mice (htau mice). We further used RNAscope and immunohistochemical assessment to validate findings of primary interest. Results We find that the DRN of htau mice differentially expresses AD-related genes, including those related to kinase binding, ion channel activity, ligand-receptor interactions, and regulation of serine/threonine kinases. We further find that computational sub-clustering of the DRN is consistent with previous circuitry-driven characterizations, allowing for spatial bounding of distinct subregions within the DRN. Of these, we find the dorsolateral DRN is preferentially impacted by 5-HT neuron loss and development of tau pathology, which coincides with increased expression of the long noncoding RNA Map2k3os. Conclusions Map2k3os may serve regulatory roles relevant for tau phosphorylation and warrants further investigation to characterize its interactions. Overall, this report demonstrates the power of large-scale spatial transcriptomics technologies, while underscoring the need for convergent-data validation to overcome their limitations.
Mediation effect of neuropsychological factors on the relationship between social networks and mild cognitive impairment in older adults
Authors: Wan Ruihan , Tu Jingnan , Gao Jiahui , Cao Lei , Zhang Lin , Huang Jia , Liu Zhizhen 
Published: November 2024

Background Although links between social networks and mild cognitive impairment (MCI) have been suggested. The pathway between social networks and MCI from the Person-Environment-Occupation (PEO) model perspective among older adults remains inconclusive. Objective To examine the relationship between social networks and MCI, and further identify whether neuropsychological factors mediate the relationship. Methods 1036 participants aged 55 to 75 years were recruited from two districts of Fuzhou, China, from December 2020 to December 2022. Data were obtained via a face-to-face neuropsychological scale assessment. Social networks and cognitive function were assessed by the Lubben Social Network Scale and the Montreal Cognitive Assessment, respectively. The mediation model and structural equation model (SEM) pathway analysis were used to examine the direct and indirect effects of social networks on MCI via neuropsychological factors. Results Data from 580 participants were analyzed (year: 65.16 ± 5.38). Regression analysis indicated that higher levels of social networks and psychological resilience were positively correlated with improved cognitive function, even after adjusting for demographic data. Increased depressive symptoms and poor sleep quality were linked to cognitive decline. Support from family members had a greater impact than support from friends in reducing the risk of developing MCI. The SEM model supported the hypothesis that significant indirect effects of social networks on MCI via psychological resilience, depressive tendencies, and sleep quality. Conclusions The effects of social networks on MCI are mediated by psychological resilience, depressive tendencies, and sleep quality.
Spirituality in social work practice: Myth or essential component of ethical and effective service provision?
Authors: Hodge David R , Boynton Heather M , Vis Jo-Ann , Graham John R , Coholic Diana , Canda Edward R 
Published: November 2024

Summary Recent scholarship questions the concept of practitioners addressing spirituality in social work practice arguing, for instance, that social workers should not conduct spiritual assessments. This article responds to these criticisms. Employing a modified domain-based review of the relevant literature, this article contends that addressing spirituality is an essential component of ethical and effective service provision. Findings To support the notion that social workers should address spirituality in practice, seven intertwined rationales are delineated. Specifically, conducting a spiritual assessment positions practitioners to (1) observe widely affirmed social work ethical principles, (2) respect client autonomy regarding the nature of the services they receive, (3) identify potential strengths that can be leveraged to assist clients deal with challenges, (4) provide culturally relevant services that resonate, rather than conflict, with clients' values, (5) create evidence-informed spiritual interventions that ameliorate problems, (6) advocate for social justice and clients' fundamental human rights, and (7) comply with professional standards and protocols that require the administration of spiritual assessments to optimize the effectiveness of services. Applications Based on the findings, we suggest that social workers should be equipped and trained to administer spiritual assessments and work with clients' spiritual and religious beliefs and practices to ensure the provision of effective, client-centered services.
Discharge Pain Medications: Do They Affect 6-Month Patient-Reported Outcomes After Operative Treatment of CMC Arthritis?
Authors: Wegner Mariah N. , Kleismith Rebekah M. , Doxey Stephen A. , Sibley Andrew , Husband Jeffrey B. , Bohn Deborah C. , Cunningham Brian P. 
Published: November 2024

Background: The purpose of this study is to analyze the relationship between discharge opioids after operative treatment of carpometacarpal (CMC) arthritis and patient-reported outcomes (PROs) over a 6-month episode of care. Methods: A total of 172 patients met inclusion criteria for this study. Patient-reported outcomes including patient-reported wrist/hand evaluation (PRWHE), single assessment numeric evaluation, and PRO measurement information system (PROMIS) global-10 questionnaires were collected prospectively and stored in an electronic data capture system until review for the purpose of this study. Morphine milligram equivalents (MMEs) were calculated using a Centers for Disease Control and Prevention-published opioid conversion table. Results: Of the 172 patients who met inclusion criteria for this study, 121 (70.4%) were female. The average patient age on the day of procedure was 63.6 ± 7.4 years. All patients received a prescription pain medication upon discharge with an average of 191.3 MMEs (range: 40.00-800.00 MMEs) prescribed per patient. Overall, there was no correlation between the amount of pain medication prescribed in MMEs and change in PROs between baseline, 6-weeks, 3-months, and 6-months ( r < .14). Discussion: Surgeons should feel confident limiting postoperative opioid prescription for patients after CMC arthroplasty without jeopardizing outcomes.
Soft partial release of non-aggressive stent retriever technique for very distal arterial occlusion stroke
Authors: Sporns Peter B , Almohammad Mohammad , Puskas Zoltan , Soda Hassan , Nguyen-Kim Thi Dan Linh , Simon Ole , Timmermann Lars , Kemmling André 
Published: November 2024

Background Endovascular thrombectomy (EVT) for very distal vessel occlusion (DVO) stroke is increasingly performed but there is insufficient evidence on the efficacy and safety of distal EVT techniques. We hypothesized that the technique of soft partial release of non-aggressive stent retrievers (SPORNS) reduces friction on the perforating vessels during thrombectomy and thereby reduces bleeding complications. Methods Retrospective study including consecutive DVO patients who were treated with the SPORNS technique between 1 January 2022 and 31 December 2022 at two tertiary stroke centers. DVOs were defined as isolated occlusions of the M3 and M4 segments of the middle cerebral artery, occlusions of the A2 and A3 segments of the anterior cerebral artery, and occlusions of the P2 and P3 segments of the posterior cerebral artery or of the superior cerebellar artery. The technique is described in detail and procedural and clinical outcomes are given. Results Twenty-four patients were treated with the SPORNS technique of whom 22 (92%) had complete or near complete recanalization (eTICI 2c/3). National Institutes of Health Stroke Scale (NIHSS) decreased from a median of nine (IQR 7–13) at admission to three (1–5) at discharge and 18 patients (75%) achieved a good outcome (modified Rankin scale 0-2) at day 90 post-stroke. Two patients (8%) had a small subarachnoid hemorrhage and two patients (8%) had a symptomatic intracerebral hemorrhage on follow-up imaging. Conclusion For the treatment of very distal arterial occlusions, the SPORNS technique employing a soft partial release of a non-aggressive stent retriever is safe and effective for the thrombectomy of small clots. The technique potentially yields a lower rate of subarachnoid hemorrhages while achieving an excellent rate of complete and first-pass recanalization.
Galvanising social innovation in gambling harms reduction: a process evaluation of a multi-component Community of Practice
Authors: Mills Thomas , Evans Jo , Jenkins Catherine L. , Grimes James , Reavey Paula , Wills Jane , Sykes Susie 
Published: November 2024

Background: Communities of Practice (CoPs) are increasingly used in health and non-health sectors globally. Evidence suggests that CoPs can support health promotion activities, but the research mainly encompasses formal, professional contexts: the role and contribution of CoPs in community-centred health promotion has not been explored. This paper presents a process evaluation of a CoP that aimed to facilitate social innovation among voluntary, community, faith and social enterprise (VCFSE) organisations. Hosted by a city-region government in England, VCFSE organisations were invited to join a CoP to enable the development and implementation of their ideas for addressing gambling harms. Methods: The process evaluation sought to develop mid-level programme theory for the use of CoPs in community-centred health promotion. Data collection consisted of 33 qualitative interviews with stakeholders, as well as project reporting. Data were organised using a framework approach which supported the construction of themes and a complex intervention model. The research team reflected on these to develop the programme theory. Results: The CoP facilitated the development of community-centred interventions for addressing gambling harms through a two-track process: first, a community of VCFSE staff was formed, whose understanding of gambling harms was nurtured through discussions led by people with Lived Experience; second, the CoP contributed to project development via collaboration, knowledge sharing and an integrated referral pathway, although project-level benefits were uneven. Learning was generated in community engagement, training, education, support and social campaigns. Conclusions: The findings confirm the combined effectiveness of a CoP, varied VCFSE projects and people with Lived Experience to co-create an evolving knowledge-base for a city-region government’s gambling harms reduction strategy. CoPs may therefore complement partnership working in community settings, although additional training support may be required in comparison with CoPs involving health professionals. The city-region government’s approach could be replicated in other emerging public health areas.