bluuebunny/crossref_metadata_2025_split huggingface dataset:
Body size and weight status of adult Indian males born in the 1890s–1950s: Age and secular change in the context of demographic, economic, and political transformation
Authors: Liczbińska Grażyna , Gautam Rajesh K. , Bharati Premananda , Malina Robert M. 
Published: June 2023

AbstractObjectivesTo evaluate secular change in body size and weight status of adult Indian males born in 1891–1957 and surveyed in the 1970s.MethodsData are from Anthropological Surveys. Only men were included in the surveys due to high female illiteracy and lack of female researchers. Indian society was also strongly conservative at the time, especially in rural areas, and the measurement of women by men was not permitted. Heights and weights of 43 950 males 18–84 years (born 1891–1957) were measured. The BMI was calculated; weight status of individuals was classified relative to WHO criteria and suggested criteria for the Asia‐Pacific region. Heights of men 35+ years were also adjusted for age‐related stature loss. Trends in measured and adjusted heights, body weight and the BMI, and in weight status were evaluated by age groups. Linear regression of measured height and adjusted height on year of birth was used to estimate secular effects.ResultsMean heights declined slightly with age to 50 years and declined sharply through 60+ years, while mean weights increased into the 40s and then declined. Mean BMIs were relatively stable from 30 to 60 years. The prevalence of thinness and normal weight was high, while that of overweight and obesity was low. Regression analyses indicated limited secular change across the total range of birth years but suggested a decline in adjusted heights among men born in 1891 through the 1930s, and little change among men born subsequently.ConclusionsAge‐related trends and results of the regression analyses by year of birth indicated negligible secular change in heights of Indian men 18–84 years born between 1891 and 1957. BMIs indicated a high prevalence of thinness and normal weight and low prevalence of overweight and obesity.
Not just snot: Local inflammatory profiles in patients with aspirin‐exacerbated respiratory disease differ from patients with aspirin‐tolerant chronic rhinosinusitis
Authors: Chiang Simon , Yu Sophie E. , Athni Tejas S. , Bergmark Regan W. , Maxfield Alice Z. , Roditi Rachel E. , Buchheit Kathleen M. , Lundberg Marie , Mitchell Margaret B. , Lee Stella E. 
Published: June 2023

Key Points
IL‐5, CCL2, and CXCL8 in sinus mucous are higher in patients with AERD relative to aspirin‐tolerant patients with CRS
These mediators are pleiotropic, leading to widescale inflammatory processes contributing to AERD
AERD is not only a T2 disease but heterogeneous: this may explain the refractory nature of AERD
Abnormal resting state EEG and vigilance in neurodegenerative dementias
Authors: Babiloni Claudio ,   Workgroup of the PDWAVES Consortium at www.pdwaves.eu
Published: June 2023

AbstractBackgroundAlzheimer’s disease dementia (ADD) is the most common neurodegenerative dementing disorder explaining about 60‐70% of 50 million patients worldwide (www.who.int). Dementia with Lewy Bodies (DLB) is another diffuse neurodegenerative dementing disorder inducing abnormalities in vigilance (visual hallucinations, cognitive fluctuations, and REM sleep behavior disorder). These abnormalities may be reflected in the reduction in amplitude (“reactivity”) of resting‐state EEG (rsEEG) alpha rhythms (7‐9 Hz) in posterior cortical areas from eye‐closed to ‐open conditions. Indeed, this “reactivity” probes cholinergic inputs from the basal forebrain to thalamocortical mechanisms regulating vigilance. The present study tested such a hypothesis.MethodClinical and rsEEG rhythms in demographic‐ and age‐matched AD (N = 48), DLB (N = 42), and healthy cognitively unimpaired (Nold, N = 38) persons were enrolled. Pathological groups were matched as cognitive status (i.e., dementia grade). The eLORETA freeware estimated rsEEG alpha cortical sources on individual basis.ResultThere was a substantial (> ‐10%) reduction in the posterior alpha source activities from the eyes‐closed to the eyes‐open condition in 93% of the Nold seniors, 77% of the ADD patients, and 64% of the DLB patients. In these participants, there was less reactivity of the posterior rsEEG alpha source activities in the ADD and DLB groups than in the Nold group. Furthermore, there was less reactivity of the occipital rsEEG alpha source activities in the DLB than in the ADD group (p < 0.05 corrected; Figure 1).ConclusionThese novel results suggest that neurophysiological oscillatory mechanisms regulating cortical arousal in the visual system during changes in vigilance may be more abnormal in DLB than ADD patients with dementia, possibly concurring to visual misperceptions, hallucinations, and vigilance fluctuations reported in DLB patients as a function of cholinergic functional connectivity to visual cortical areas. Furthermore, the present results suggest that many DLB patients may suffer from a pathological transition from “reactive” posterior rsEEG alpha rhythms during eye‐opening to “unreactive” theta rhythms becoming a dominant background frequency. Importantly, this transition may be erroneously considered as “alpha” if the reactivity of those rsEEG rhythms is not tested during both eyes‐closed and ‐opening conditions.
Associations of time in bed and sleep timing with dementia and cognitive decline among Chinese rural‐dwelling older adults: A cohort study
Authors: Liu Rui , Ren Yifei , Dong Yi , Wang Yongxiang , Cong Lin , Hou Tingting , Wang Xiang , Sindi Shireen , Tang Shi , Du Yifeng , Qiu Chengxuan 
Published: June 2023

AbstractBackgroundThe longitudinal associations of time in bed (TIB) (a composite indicator of sleep duration, latency, and fragmentation) and sleep timing (a marker of circadian rhythms) with dementia and cognitive decline in older adults are unclear.MethodThis population‐based cohort study used data from 1982 participants in the Shandong Yanggu Study of Aging and Dementia, who were aged ≥60 years, free of dementia, and living in the rural communities in western Shandong Province, China. At the baseline (2014) and follow‐up (2018) examinations, sleep parameters were assessed using the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale. Global cognitive function was measured using the Mini‐Mental State Examination (MMSE). Dementia was diagnosed following the DSM‐IV criteria, and the NIA‐AA criteria for Alzheimer disease (AD). Data were analyzed using restricted cubic splines, Cox proportional‐hazards models, and general linear models.ResultDuring the mean follow‐up of 3.7 (standard deviation = 0.3) years, dementia was diagnosed in 97 participants (68 with AD). Restricted cubic spline curves showed J‐shaped associations of sleep duration, TIB, and rise time with dementia risk, and a reverse J‐shaped association with mid‐sleep time. When continuous sleep parameters were categorized into tertiles, the multivariable‐adjusted hazard ratio (HR) of incident dementia was 1.69 (95%CI 1.01‐2.83) for baseline sleep duration >8 hours (vs. 7‐8 hours), 2.17 (1.22‐3.87) for bedtime before 9PM (vs. 10PM or later), and 2.00 (1.23‐3.24) for mid‐sleep time before 1AM (vs. 1‐1.5AM). Early bedtime and mid‐sleep time were significantly associated with incident AD (multivariable‐adjusted HR range: 2.25‐2.51; P<0.05). Among individuals who were free of dementia at follow‐up, baseline long TIB, early bedtime and mid‐sleep time, early and late rise time, and prolonged TIB and advanced mid‐sleep time from baseline to follow‐up were associated with greater decline in MMSE score (P<0.05). These associations with cognitive decline were statistically evident mainly among men or participants who were aged <75 years.ConclusionLong TIB and early sleep timing are associated with an increased risk of dementia and AD, and their associations with greater cognitive decline are evident only among young‐old people and men.
First MRI impact on belief revision and decision making in FTD diagnostic evaluation
Authors: Montplaisir Samuel , Ducharme Simon , de Boer Sterre C.M. , Pijnenburg Yolande A.L. ,   Neuropsychiatric International Consortium on Frontotemporal Dementia
Published: June 2023

AbstractBackgroundMRI has a central value in frontotemporal dementia (FTD) diagnostic workup. We set out to examine how MRI results impact FTD cases workup and clinician belief revision.MethodQuestionnaire to Neuropsychiatry International Consortium Frontotemporal Dementia (NIC‐FTD) members in February 2021 (n = 23) with follow‐up questionnaire in June 2021 (n = 13).ResultAbout 90.9% of respondents indicated that a first MRI would exclude a diagnosis of FTD in less than 20% of cases. About 59.1% of clinicians indicated that over 60% of their FTD cases were confirmed with the first MRI (22.7% indicated that between 40% and 60% of cases were confirmed with the first MRI and 18.2% indicated that less than 40% of cases were confirmed with the first MRI). Those who felt most of their FTD cases were confirmed with a first MRI preferred a second MRI as follow‐up imaging (69.2%) rather than PET imaging (30.8%). Those who felt most of their FTD cases were not confirmed with a first MRI preferred PET scan (75.0%) over a second MRI (25.0%). The first MRI ended less than 20% FTD investigations for 55.6% or clinicians and ended less than 40% FTD investigations for 77.8% clinicians. About 91.3% of respondents indicated that the first MRI impacted which tests they would order next (table 1.) About 77.8% of clinicians indicated that the first MRI lead to belief revision in less than 40% of FTD cases and 44.4% indicated belief revision in less than 20% of cases.ConclusionThere is discrepancy between first MRI impact on belief revision compared to its impact on FTD cases workup. Rather than being a Bayesian oddity, this illustrates the distinction between belief revision and acceptance attitudes revision, which refers to how we follow clinical guidelines independently of our own beliefs. Social desirability bias is also relevant: respondents might want to indicate they feel confident in their intuition regarding FTD diagnosis while still ordering tests that are expected. Current limitations include sample size and aforementioned bias. Further research into belief revision, how the first MRI impact FTD investigation algorithm, and how to volumetric imaging can supplement MRI interpretation may also be warranted.
Amyloid accumulation and functional connectivity in normal aging and preclinical Alzheimer’s Disease: a longitudinal analysis of the OASIS‐3 cohort
Authors: Zhukovsky Peter , Moffat Gemma L , Coughlan Gillian , Voineskos Aristotle N. 
Published: June 2023

AbstractBackgroundPathological changes in the brain begin accumulating decades before the appearance of cognitive symptoms in Alzheimer’s Disease (AD). The deposition of amyloid‐beta (Aβ) proteins and other neurotoxic changes occur, leading to disruption in functional connections between brain networks. Discrete characterization of the changes that take place in preclinical AD has the potential to help treatment development by targeting the neuropathological mechanisms to prevent cognitive decline and dementia from occurring entirely. Previous research has focused on cross sectional differences in the brains of patients with mild cognitive impairment (MCI) or AD and healthy controls or has concentrated on the stages immediately preceding cognitive symptoms. The present study emphasizes early preclinical phases of neurodegeneration.MethodWe use a longitudinal approach to examine the brain changes that take place during early stages of cognitive decline in the OASIS‐3 dataset. Among 1098 participants, 274 passed the inclusion criteria (i.e. had at least two repeated measures of cognitive status and amyloid levels). We use mixed‐effect linear models to examine rates of amyloid accumulation in those who showed cognitive decline compared to those who did not change in cognitive status.ResultOver 90% of participants were healthy at baseline. Over 8‐10 years, some participants progressed to very mild dementia (n = 48) while others stayed healthy (n = 226). Participants with cognitive decline have faster amyloid accumulation and greater increases in functional connectivity in similar brain regions, namely among lateral temporal, motor, and some lateral prefrontal cortex areas. These changes were linked to increases in functional connectivity of select default mode, frontoparietal and motor components.ConclusionOur findings advance the understanding of initial amyloid staging in preclinical Alzheimer’s, as well as contribute to the determination of the functional changes that occur among brain network components as the disease progresses.
Neuronal, glial and microglial maps of epigenetic and transcriptomics dysregulations in Alzheimer’s disease
Authors: Bendl Jaroslav , Girdhar Kiran , Hauberg Mads E , Zeng Biao , Kosoy Roman , Dong Pengfei , Rahman Samir , Kleopoulos Steven P , Voloudakis Georgios , Hoffman Gabriel E , Fullard John F , Roussos Panos 
Published: June 2023

AbstractBackgroundRegions of open chromatin house regulatory elements required to mediate cell‐type and tissue‐specific gene expression. Human brain studies have shown that dysregulation of these regulatory mechanisms is associated with Alzheimer’s Disease (AD). Here, we present the largest cell type and brain region‐specific differential chromatin accessibility analysis and fine‐mapping analysis in AD.MethodUsing both fresh and frozen postmortem tissue from over 200 cases with AD and controls, we performed ATAC‐seq to profile chromatin accessibility in three distinct populations of cells (neurons, glia, and microglia), isolated by FACS from three brain regions. We characterized epigenetics changes associated with multiple AD phenotype ratings. We further studied the correlation structures in chromatin accessibility to define high‐resolution maps of cis‐regulatory domains. Lastly, we examined population‐level variation of gene expression and chromatin accessibility to pinpoint genetically driven regulation of transcription.ResultWe observed widespread differences in chromatin accessibility associated with AD. The differential cis‐regulatory domains were highly concordant with gene expression perturbations suggesting coordinated changes of the 3D genome regulation of the transcriptome in AD. For microglia cells, the fine‐mapping analysis identified putative regulatory mechanisms for 21 AD risk loci, of which 18 were refined to a single gene, including 3 novel genes (KCNN4, FIBP and LRRC25). Transcription factor regulatory networks captured AD risk variation and identified SPI1, IRF1, and PURA as the key regulators of microglia expression changes in AD. The same analysis in neurons pinpointed upstream transcription factor 2 (USF2), which regulates the genes participating in lysosome function, which we validated by overexpression and knockdown experiments. Lastly, we determined enhancer‐promoter interactions, by generating additional omics in brain tissue (Hi‐C, H3K27ac ChIP‐seq) and jointly analyzing with ATAC‐seq based on the “activity‐by‐contact” approach. To prove the relevance of these putative enhancers, we performed validations in neuronal progenitor cells.ConclusionOverall, our human neuronal, glia, and microglia multi‐scale omics datasets uncovered disease‐associated perturbations impacting chromatin accessibility, transcription factor regulatory networks, and the 3D genome, and implicated transcriptional dysregulation in AD. Furthermore, we were able to fine‐map multiple AD loci, identifying not only the relevant genes but, in some cases, proposing the regulatory mechanisms contributing to disease.
Relationships between polymorphisms in EPHX2, CYP2J2, CYP2C9, and CYP2C8, white matter hyperintensities, and regional atrophy
Authors: Wong Yuen Yan , Yu Di , Xiong Lisa Y. , Mirza Saira S. , Rogaeva Ekaterina , Chenoweth Meghan J. , Ramirez Joel , Scott Christopher J. M. , Holmes Melissa F. , Gao Fuqiang , Symons Sean , Heyn Chinthaka Chris , Lam Benjamin , Zukotynski Katherine , Bhan Aparna , Swartz Richard H. , Sahlas Demetrios J. , Black Sandra E. , Masellis Mario , Swardfager Walter 
Published: June 2023

AbstractBackgroundWhite matter hyperintensities (WMH) of presumed vascular origin commonly coincide with neurodegeneration. Previous studies reported heterogeneous relationships between WMH and atrophy. Cytochrome P450s CYP2J2, CYP2C8, and CYP2C9 are involved in the vascular ischemic response and soluble epoxide hydrolase (EPHX2) metabolizes its products, which have been implicated in vascular pathology. Here we investigate potential effects of single nucleotide polymorphisms (SNPs) in these genes on WMH and atrophy.MethodPatients with vascular cognitive impairment and/or neurodegenerative diagnoses were drawn from the Sunnybrook Dementia Study (NCT01800214), Vascular Brain Health (VBH) study, and the Brain‐Eye Amyloid Memory (BEAM) study. SNPs were genotyped using the Illumina Neurochip. Patients of European ancestry confirmed via principal components analysis were included. Variants in candidate genes were identified by variant IDs from dbSNP. Linkage‐disequilibrium‐based clumping on minor allele frequency (MAF) was applied via PLINK v1.9 (LD threshold: 0.2) to prioritize SNPs with higher MAF (removing SNPs with MAF<10%). Imaging (T1, T2/PD and FLAIR) was acquired at 3.0T for volumetric analysis using an in‐house segmentation (SABRE/Lesion Explorer). Linear regression models controlling for age, sex, Mini Mental State Exam, and head size were used to assess effects of the SNPs on WMH or atrophy, and effects of SNP×WMH interactions on atrophy in R. Genotypes were coded additively.ResultAmong included participants (n = 508, 71±11 years, 51% female), EPHX2 rs2741351 C/A (MAF = 16%) was associated with frontal (F = 3.54, p = 0.030), temporal (F = 5.86, p = 0.003), and global (F = 6.18, p = 0.002) atrophy. CYP2J2 C/T rs11572214 was associated with frontal (F = 3.99, p = 0.019) and global (F = 4.13, p = 0.017) atrophy. CYP2C8 rs11572174 G/A (MAF = 12%) was associated with deep WMH (F = 3.71, p = 0.025). EPHX2 rs2279591 C/T (MAF = 28%) moderated the association between periventricular WMH and temporal atrophy (F = 5.48, p = 0.004); CYP2C9 rs6583964 G/A (MAF = 47%) moderated the association between periventricular WMH and frontal atrophy (F = 3.74, p = 0.024); and CYP2J2 rs11572214 (MAF = 42%) moderated the association between deep WMH and temporal atrophy (F = 3.58, p = 0.029).ConclusionGenetic variation in the CYP450‐soluble epoxide hydrolase pathway was related to WMH and brain atrophy in people with cognitive impairment. The results suggest that this pathway may contribute to small vessel cerebrovascular disease, and to its impact on neurodegeneration.
Ferrostatin‐1 and z‐VAD‐FMK Potentially Attenuated Iron‐mediated Neurotoxicity and Rescued Cognitive Function in Iron‐overloaded Rats
Authors: Sripetchwandee Jirapas , Kongkaew Aphisek , Kumfu Sirinart , Chunchai Titikorn , Chattipakorn Nipon , Chattipakorn Siriporn C 
Published: June 2023

AbstractBackgroundOur study indicated that iron‐overloaded condition induced neurotoxicity in rats and cognitive impairment (1). Furthermore, neuronal deaths caused by apoptosis and ferroptosis, have been identified as one of the underlying mechanisms of neurotoxicity in iron‐overloaded condition (1, 2). Recently, a ferroptosis inhibitor; ferrostatin‐1 and a pan‐caspase inhibitor; z‐VAD‐FMK exerted neuroprotection in traumatic brain injury and intracerebral hemorrhagic brain. Nonetheless, the comparative efficacy of these cell death inhibitors on brain parameters and cognitive function in iron‐overloaded rats has not yet been investigated.MethodThirty male Wistar rats were divided into 2 groups to receive an intraperitoneal injection with 10% dextrose in normal saline solution (NSS) as a control group (n = 6) or 100 mg/kg iron dextran as an iron‐overloaded group (n = 24). After 4 weeks of injection, iron‐overloaded group was subdivided into 4 groups (n = 6/ group) to subcutaneously receive with the pharmacological interventions including 1) vehicle (10% DMSO in NSS), 2) deferoxamine (25 mg/kg), 3) ferrostatin‐1 (2 mg/kg), and 4) z‐VAD‐FMK (1 mg/kg). In contrast, rats in the control group were received vehicle. Those mice were received the assigned treatment for further 2 weeks. Behavioral tests including the Morris water maze test (hippocampal‐dependent memory) and novel object recognition test (hippocampal‐independent memory), were performed. At the end of experiments, systemic iron overload and brain parameters including blood‐brain tight junction proteins, brain iron, synaptic markers, and brain ferroptosis/apoptosis were determined.ResultNot only systemic iron overload, but iron‐overloaded rats exhibited blood‐brain barrier breakdown, brain iron overload, iron‐mediated brain toxicity including brain oxidative stress, loss of synaptic proteins, and brain ferroptosis/apoptosis, leading to cognitive impairment. Treatment with deferoxamine attenuated rats from systemic iron overload, brain pathologies, and hippocampal‐independent memory (Figure 1A), but failed to rescue hippocampal‐dependent memory in iron‐overloaded rats (Figure 1B). Interestingly, cell death inhibitors including ferrostatin‐1 and z‐VAD‐FMK provided superior neuroprotection than deferoxamine by attenuating loss of synaptic proteins and restoring cognitive function in hippocampal‐dependent and hippocampal‐independent manners (Figure 1A‐1C).ConclusionFerrostatin‐1 and z‐VAD‐FMK exerted neuroprotective effects and cognitive restoration in rats under iron‐overloaded condition, suggesting the novel therapeutic strategy using cell death inhibitors in brain following iron‐overloaded condition.