bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Relationship Between LRP-5 and LRP-6 Gene Mutations and Postmenopausal Type 2 Diabetes and Obesity
Authors: Li Jun , Li Ya , Lu Yunqiu , Li Siyuan , Zhu Yecheng , Sun Chuanbing , Rai Partab , Jia Xuehai 
Published: January 2025

Background: Single nucleotide polymorphisms (SNPs) in the low-density lipoprotein receptor-related protein 5 (LRP5) and the low-density lipoprotein receptor-related protein 5 (LRP6) genes have been implicated in the pathogenesis of type 2 diabetes mellitus (T2DM) and obesity (OB). This study aimed to evaluate the polymorphisms in LRP5 and LRP6 genes in postmenopausal patients with T2DM and OB. Methods: Participants were categorized into the Non-T2DM group (n = 53) and the T2DM group (n = 89) based on glycemic levels. Baseline data and biochemical indices were collected, Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry, and SNPs at the LRP5 and LRP6 loci were assessed by time-of-flight mass spectrometry. Results: 1. There was a statistical difference in the distribution of genotypes (CC/CT) at locus rs4988331 (χ2 = 67.940, P = .000) and in the distribution of alleles (C/T) between the T2DM and non-T2DM groups (χ2 = 50.506, P = .000). Additionally, there were significant differences in the allele (G/A) at locus rs11054704, and both allele (G/T) and genotype (GG/GT) distributions at locus rs1181334 between the OB group and the normal weight group ( P < .05). 2. OB was identified as a risk factor for T2DM in individuals with the wild-type at locus rs1181334, and the interaction between wild-type and mutant was significant ( P < .05). 3. Multifactorial logistic regression analysis revealed that BMD (OR 3.755; 95% CI, 1.215-11.608) and triglyceride-glucose (TyG) index (OR 2.855; 95% CI, 1.361-5.986) were risk factors for T2DM in postmenopausal women, whereas alkaline phosphatase (ALP; OR 0.970; 95% CI, 0.945-0.995) and rs4988331 mutation (OR 0.018; 95% CI, 0.006-0.060) were protective factors. Conclusion: Mutations at the LRP5-rs4988331 locus, as well as the LRP6-rs11054704 and rs1181334 loci, may be associated with the development of T2DM and OB in postmenopausal women.
Di Huang Yi Zhi Fang improves cognitive function in APP/PS1 mice by inducing neuronal mitochondrial autophagy through the PINK1-parkin pathway
Authors: Zhang Limin , An Hongmei , Zhen Rongrong , Zhang Tong , Ding Minrui , Zhang Mengxue , Sun Yiguo , Gu Chao 
Published: January 2025

Background Alzheimer's disease (AD) is an irreversible age-related neurodegenerative condition characterized by the deposition of amyloid-β (Aβ) peptides and neurofibrillary tangles. Di Huang Yi Zhi (DHYZ) formula, a traditional Chinese herbal compound comprising several prescriptions, demonstrates properties that improve cognitive abilities in clinical. Nonetheless, its molecular mechanisms on treating AD through improving neuron cells mitochondria function have not been deeply investigated. Objective This study administered DHYZ to APP/PS1 mice to explore its potential therapeutic mechanisms in AD treatment. Methods APP/PS1 transgenic mice were given DHYZ (L, M, H), donepezil, or distilled water for a consecutive 12-week period. The Morris water maze test was used to assess memory capacity, transmission electron microscopy was used to observe mitochondrial and synaptic structures, immunohistochemistry and western blot detected proteins involved in the mitochondrial autophagy pathway, ELISA measured serum Aβ content, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assessed neuronal cell apoptosis. Results DHYZ demonstrates a notable therapeutic impact on mice with AD, effectively improving cognitive and memory impairments. DHYZ decreases Aβ accumulation in the hippocampus by reducing BACE1 activity and enhancing Aβ clearance through the blood-brain barrier. Additionally, DHYZ significantly suppresses neuronal apoptosis, enhances synaptic structure, and increases synapse numbers, processes strongly linked to the activation of mitochondrial PINK1-Parkin autophagy. Conclusions DHYZ enhances cognitive function in APP/PS1 mice by stimulating neuronal mitochondrial autophagy through the PINK1-Parkin pathway.
Immune cells: Mediators in the metabolites and Alzheimer’s disease
Authors: Zhang Erdong , Dai Fengqiu , Tao Ling , Chen Yanqin , Chen Tingting , Shen Xiangchun 
Published: January 2025

Background Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that predominantly affects elderly individuals across the globe. While genetic, environmental, and lifestyle factors are known to influence the onset of AD, the underlying mechanisms remain unclear. Objective To elucidate the intricate interplay between metabolites and immune cell activation in the ethology of AD, and to determine their collective impact on AD risk. Methods We conducted a comprehensive analysis of genome-wide association studies data to examine the relationships between metabolites, immune cell phenotypes, and the risk of AD. Our study encompassed a comprehensive examination involving 731 distinct immune cell types, 1400 metabolites, and a large cohort comprising10,520 AD cases with 401,661 controls. We employed univariate Mendelian randomization to assess bidirectional relationships between metabolites and AD, metabolites and immune cells, as well as immune cells and AD. Subsequently, multivariate Mendelian randomization was then applied to evaluate the potential mediating role of immune cells on the relationship between metabolites and AD. Results Specific metabolites, the histidine/pyruvate ratio and homoarginine, were positively associated with the risk of AD, mediated by immune cells. Conversely, 4-hydroxycoumarin and glycolithocholate sulfate showed protective associations against AD. Immune cell markers, CD64 on monocytes and HLA DR on CD14+ CD16− monocytes were linked to higher AD risk, while CD33dim HLA DR+ CD11b− myeloid cells and HLA DR on CD8+ T cells were protective. Conclusions This study highlights the critical role of immune cells in the pathogenesis of AD, demonstrating how their interaction with specific metabolites influences disease risk.
Differences in brain volume in individuals with mild cognitive impairment and normal cognition across different anatomical regions: The Atherosclerosis Risk in Communities (ARIC) study
Authors: Mijares Diaz Fernando , Orlando Alessandro , Schneider Andrea LC , Pike James R , Jack Clifford R , Deal Jennifer A , Sharrett A Richey 
Published: January 2025

Background Mild cognitive impairment (MCI) represents a stage between cognitively normal and Alzheimer's disease. Despite much published research on MCI, there continues to be a knowledge gap of volumetric brain changes in MCI versus cognitively normal (CN) in racially diverse, community-based samples. Objective The study aimed to understand differences in volume of selected brain regions in individuals with MCI versus those who are cognitively normal. Methods This was a cross-sectional study with 1835 participants, which sampled all cognitively impaired participants (n = 667) and a subsample of cognitively normal participants from the ARIC neurocognitive study (ARIC-NCS). All individuals underwent a brain MRI. Two models (5 versus 22 regions of interest [ROI]) were built to analyze differences in brain volume between cognitively normal and MCI, and among 3 cognitive domains (memory, language, executive function). Using previous visits data, we estimated the standard deviations of 20-year cognitive decline equivalent to the difference in brain volume between MCI and CN. Results Every lobe was significantly smaller in individuals with MCI, with the largest difference observed in the temporal lobe. Moreover, there was a significant difference between MCI and CN in every subregion within the temporal lobe. The difference in volume between CN and MCI was equivalent to the total brain volume difference associated with a 1.24 standard deviation greater long-term cognitive decline. Conclusions Loss of volume in all cortical lobes, but particularly in the temporal lobe, was associated with MCI. Additionally, significant volume differences were observed in the temporal lobe in all three cognitive domains.
Cognivue Clarity® characterizes amyloid status and preclinical Alzheimer's disease in biomarker confirmed cohorts in the Bio-Hermes Study
Authors: Galvin James E , Kleiman Michael J , Estes Paul W , Harris Heather M , Fung Ernest 
Published: January 2025

Background Cognivue Clarity® is an FDA-cleared computerized cognitive test to screen for cognitive impairment included in the Bio-Hermes Study to test blood-based and digital biomarkers’ ability to screen for mild cognitive impairment (MCI) and Alzheimer's disease (AD). A subset of cognitively normal individuals have amyloid deposition (Preclinical AD) but no current assessment can identify these individuals in the absence of expensive biomarkers. Objective We examined differences in Cognivue Clarity performance between amyloid positive and amyloid negative individuals and whether Cognivue Clarity could differentiate True Controls (cognitively normal/amyloid negative), Preclinical AD (cognitively normal/amyloid positive), and MCI due to AD (MCI-AD, cognitively impaired/amyloid positive). Methods Cognivue Clarity was administered to all participants in the Bio-Hermes Study who also had amyloid PET and blood-based biomarkers. Performance was compared between biomarker-defined groups: True Controls (n = 297), Preclinical AD (n = 95), and MCI-AD (n = 113). Results Cognivue Clarity global scores distinguished amyloid positive individuals from amyloid negative individuals ( p < 0.001) and differentiated True Controls versus Preclinical AD ( p = 0.014) and Preclinical AD versus MCI-AD ( p < 0.001). Three subtests [Shape Discrimination ( p = 0.004), Visual Salience ( p = 0.008), Adaptive Motor Control ( p = 0.004)] and the 3-test mean ( p < 0.001) differentiated True Controls from Preclinical AD. The 3-test composite correlated with Amyloid PET (r = −0.433) and pTau217 (r = −0.400). The 3-test mean identified Preclinical AD in both White and Black participants. Conclusions Cognivue Clarity, a 10-min computerized battery, screens for individuals with cognitive impairment, characterizes amyloid positive individuals, and identifies Preclinical AD. This has great potential as a cost- and time-effective strategy to screen and enroll in AD prevention trials.
Expression of Plasma Levels of miRNA-181b and miRNA-21 in Patients With Abdominal Aortic Aneurysms and Their Effect on Clinical Outcome After Endovascular Treatment
Authors: Leite Túlio Fabiano de Oliveira , da Silva Elpidio Ribeiro , Evelyn Karoline , Tirapelli Daniela Pretti da Cunha , Joviliano Edwaldo Edner 
Published: January 2025

Introduction: Abdominal aortic aneurysms (AAA) are major causes of morbidity and mortality in the elderly population. Endovascular aneurysm repair (EVAR) is associated with lower complications rates than conventional treatment; however, rigorous follow-up with contrast imaging is required to confirm aneurysmal sac exclusion. The main objective of this study was to quantify and evaluate miRNA expression response to EVAR based on serum dosages at the 6-month follow-up. Population and Method: 47 patients with indication for EVAR were recruited and 10 patients without comorbidities. miRNA-181b and miRNA-21 were selected for this study and their serum dosages were measured at two time points: preoperatively and after 6 months of follow-up, and only once in the control group. Demographic profiles, clinical follow-ups, and imaging examinations with angiotomography performed preoperatively and after 6 months were collected. Results: Overexpression of miRNA-181b and miRNA-21 was observed in the whole blood of patients with AAA. EVAR of patients with AAA resulted in decreased expression of the studied miRNAs, indicating that exclusion of the aneurysmal sac alters the expression of these markers. In addition, the expressions of miRNAs did not correlate with endoleaks or the diameter of the aneurysm or with the different types of devices used for the EVAR. Conclusions: The overexpression of miRNA-181b, miRNA-21 with its reduction after EVAR, may suggest the use of these molecules as potential biomarkers in the follow-up of these patients. However, miRNAs were not able to identify possible endoleaks or discriminate them into subtypes. Clinical Impact The clinical application of the use of biomarkers in other areas such as oncology is already well established. In endovascular surgery it is still incipient although with great potential in daily practice, in order to anticipate or schedule possible interventions in patients with endoleak. In addition, understand the mechanisms of action of miRNAs in Atherosclerotic diseases and aortic syndromes could provide a better understanding of the pathophysiology as well as pharmacological development for AAA prevention as well as remodeling of the aneurysm sac after EVAR.
Birth Rate as a Determinant of Dementia Incidence: A Comprehensive Global Analysis
Authors: You Wenpeng 
Published: January 2025

Background The role of parity in predicting dementia risk in women is debated. This study examines how birth rate affects global dementia incidence. Methods Country-specific data on birth rate and dementia incidence rate were analyzed using bivariate analysis, partial correlation, and multiple linear regression. Confounding factors such as aging, affluence, genetic predisposition (Ibs), and urbanization were considered. Results Pearson’s r and nonparametric analyzes showed a significant inverse correlation between birth rate and dementia incidence. This relationship remained significant after controlling for aging, affluence, Ibs, and urbanization. Multiple linear regression identified birth rate as a significant predictor of dementia incidence, and as the strongest predictor. Affluence and urbanization were not significant predictors. The correlation was stronger in developing countries. Conclusions Lower birth rate is an independent risk factor for dementia, particularly in developed countries. These findings highlight the importance of considering birth rate in dementia studies.
Lifestyle Medicine and the Far Horizon: Before, Since, and Beyond
Authors: Katz David L. 
Published: January 2025

The American College of Lifestyle Medicine was founded just over 20 years ago. As the organization grew, it incubated an impressive array of structures and processes to foster professional standards, training, credentialing, networking, and scholarship. A compelling and accelerating drumbeat of peer-reviewed publications has demonstrated the advancing base of evidence in which lifestyle medicine practice is rooted. Despite all this good effort, however, the indicators of population health that matter most—longevity and vitality and healthspan, years in life and life in years—have largely trended away from, rather than toward, aspirations. The life course of ACLM has introduced an area of great allure and tremendous promise to health professionals seeking beyond reactive disease care. The processes, structures, and knowledge are in place to advance the goals of vitality and longevity at the population level. Needed, still, are the means of translating that accumulated knowledge into the power of routine, and effective action. Those of us committed to the full potential of lifestyle both in and as medicine have promises yet to keep and miles to go before we sleep. We can, however, see the light on the horizon from here.
Is there a simple and accessible solution to improve acute infarct core imaging? The utility of steady-state CT angiographic source images obtained from a delayed phase acquisition
Authors: Mortimer Alex , Flood Richard , Dunkerton Sophie , McClelland Sarah Beth , Minks David , Crossley Robert , Wareham James , Smith Aubrey , Cox Anthony , Bosnell Rose 
Published: January 2025

Background Early identification and quantification of core infarct is of importance in stroke management for treatment selection, prognostication, and complication prediction. Non-contrast computed tomography (CT) (NCCT) remains the primary tool, but it suffers from limited sensitivity and inter-rater variability; CT perfusion is inconsistently available and commonly blighted by movement artefact. We assessed the performance of a standardised form of CT angiographic source imaging (CTASI) obtained through addition of a delayed phase at 40 seconds post-contrast injection (DP40) following fast-acquisition CT angiography. Methods Contrast resolution between ischaemic and normal grey matter (GM) was compared qualitatively and quantitatively to NCCT. Using Alberta Stroke Program Early CT Score (ASPECTS), DP40 low density was compared to NCCT and venous phase CT perfusion source images (CTPSI) and to 24-hour NCCT ASPECTS in patients with timely endovascular recanalisation (Thrombolysis In Cerebral Infarction 2C/3). Results Seventy-four patients with a proximal middle cerebral artery or terminal internal carotid artery occlusion were included. The mean attenuation difference between ischaemic and normal GM increased from 4.86+/−3.12 HU (NCCT) to 9.30+/−3.14 HU (DP40) (p < 0.0001). Subjective assessment by two raters revealed that DP40 improved ischaemic tissue conspicuity in 39 to 41 (78–82%) of cases (kappa 0.805, standard error 0.108, 95% confidence interval: 0.593–1.000). The correlation between ASPECTS on baseline imaging and eventual 24-hour ASPECTS improved from R = 0.7197 for NCCT to R = 0.9875 for DP40 (z = 7.89, p < 0.0001). The correlation between DP40 and venous phase CTPSI ASPECTS was 0.9681, p < 0.0001. Conclusion DP40 CTASI represent a simple technique for improving detection and estimation of extent of ischaemia over NCCT and show close correlation with surrogate measures of infarct core.
The use of cannabidiol as adjunctive therapy in adult patients with drug-resistant epilepsy: a systematic review and meta-analysis
Authors: Ong Marjorie Jia Yi , Abd Rahman Muhammad Samir Haziq , Lee Vanessa Lin Lin , Lee Kong Heng , Chang Carmen Jia Yinn , Khoo Ching Soong , Hod Rozita , Tan Hui Jan , Trinka Eugen 
Published: January 2025

Background: Highly purified cannabidiol (CBD), recently approved for various neurological disorders, is explored as a potential therapeutic avenue for drug-resistant epilepsy (DRE) among adult people with epilepsy (PWE) in this systematic review and meta-analysis. Objectives: To conduct an extensive literature review and meta-analysis of CBD use for DRE in adult PWE. Design: Systematic review and meta-analysis. Data sources and methods: We conducted a systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and two electronic resources; we searched Ovid MEDLINE and Scopus using appropriate keywords until August 2023. Data were presented as standardized mean difference (SMD) and odds ratio with confidence interval (CI) via random effect. We appraised the risk of bias of the included studies using the Joanna Briggs Institute critical appraisal tool while their strength of evidence with the Oxford Centre for Evidence-Based Medicine (OCEBM) and Grading of Recommendations Assessment Development and Education (GRADE) Levels of Evidence. Results: We identified 16 studies, 3 of which were randomized controlled trials and 3 prospective cohort studies, while the rest were expanded access programs, deriving a total of 668 participants receiving CBD for seizure control. CBD was used concomitantly with antiseizure medications in all studies. There was a statistically significant seizure reduction in the group receiving CBD therapy compared to the placebo group (SMD: −1.50, 95% CI (−3.47, 0.47), p < 0.01). Conclusion: The evidence on CBD use in adult patients with DRE demonstrates a moderate level of certainty according to GRADE level and OCEBM level 2. Further prospective studies involving multiple centers are encouraged to study both the efficacy and safety of CBD in adult patients with DRE. Trial registration: International Prospective Register of Systematic Reviews (PROSPERO) 2023 CRD42023449955.
Outcomes of a pilot randomized clinical trial testing brief interventions to increase HIV pre-exposure prophylaxis uptake among rural people who inject drugs attending syringe services programs
Authors: Surratt Hilary L. , Brown Sarah , Burton Abby L. , Cranford Will , Fanucchi Laura C. , Green Christie , Mersch Stephanie M. , Rains Rebecca , Westgate Philip M. 
Published: January 2025

Background: Kentucky is one of seven states with high, sustained rural HIV transmission tied to injection drug use. Expanding access to pre-exposure prophylaxis (PrEP) has been endorsed as a key HIV prevention strategy; however, uptake among people who inject drugs (PWID) has been negligible in rural areas. Syringe services programs (SSPs) have been implemented throughout Kentucky’s Appalachian region, providing an important opportunity to integrate PrEP services. Objectives: The primary objective was to examine preliminary efficacy and effect sizes of the study interventions on PrEP initiation among HIV-negative PWID. Design: Parallel group randomized controlled trial. Methods: Eighty participants were enrolled from two rural SSP locations in southeastern Kentucky. Following informed consent, participants completed a baseline interview, and were randomized to the intervention comparators. The primary endpoint was PrEP initiation, measured by dispensed PrEP prescription, within the 6-month study period. Analyses employed intent-to-treat (ITT) and per protocol approaches. Results: In total, 77/80 enrollees (96.2%) completed at least one session of their assigned intervention, regardless of trial arm. Seventy (87.5%) were linked to the embedded PrEP provider for the initial clinical visit; 38 (47.5%) completed a follow-up clinical visit with the provider, 22 (27.5%) were issued a prescription, and 7 (8.8%) initiated PrEP during the study period. We observed a 12.1% difference (14.6% vs 2.5%; ITT) and 12.8% difference (15.4% vs 2.6%; per protocol) in the primary outcome (PrEP initiation), in favor of the experimental intervention. Conclusion: This pilot trial established proof of concept for integrated PrEP care within SSPs in rural areas, and demonstrated a clinically meaningful difference in PrEP initiation between interventions, which warrants examination in a larger trial. Rates of early care discontinuation indicate a need for ongoing patient engagement strategies and implementation support for community SSPs. Trial registration: Prospective registration with ClinicalTrials.gov, NCT05037513 (registered August 5, 2021).