bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences of ASL‐MRI measured cerebral blood flow among patients with AD, patients with MCI and cognitively umimpaired individuals
Authors: Zan Yunlong , Zhang Miao , Chen Kewei , Li Biao , Huang Qiu
Published: February 2022

Background

The purpose of this work is to examine the relative cerebral blood flow (CBF), via arterial spin labeling (ASL) MR imaging, in patients with Alzheimer disease (AD) and mild cognitive impairment (MCI) compared with healthy control (HC) participants.

Method

Forty‐one patient with AD (21 males, mean age, 65 years ±9, age range, 46‐84 years), 45 patients with MCI (22 males, mean age, 70 years ±9, 42‐84 years) and 19 HCs (7 males, mean age, 67 years ±6, age range, 55‐80years), determined by CDR (dementia: CDR=1/2/3, MCI: CDR= 0.5. HC: CDR=0), underwent 3T MRI scans. Pulsed ASL perfusion images were normalized to the MNI space using SPM12.

CBF images were calculated by subtracting the labeled from unlabeled normalized ASL‐MR images using FSL. We then divided CBF images by the mean CBF value in the global brain to obtain the relative CBF (rCBF) images. The statistical analysis among three groups (AD, MCI, and HC) was performed at voxel level with age, sex and education entered as confounding variables.

Result

Compared with HC, MCI patients showed rCBF reduction in right inferior occipital gyrus (P<0.005). In patients with AD compared with HC, the rCBF values significantly declined in left Hippocampus, left occipital gyrus, right inferior occipital gyrus, precuneus left thalamus and right inferior temporal region (P<0.005). Compared to the MCI group, the rCBF values in AD group decreased in left middle occipital gyrus, left precuneus and left posterior cingulum (P<0.005), while increased in superior temporal region, anterior cingulum and middle cingulum (P<0.005).

Conclusion

The transition from normal cognition to MCI and finally to AD is associated with decreases in rCBF for some brain regions. However, in other regions, the vascular compensatory process may result in rCBF increase during the transition from MCI to AD.
Association between brain reserve proxies and clinical progression in Alzheimer’s disease dementia
Authors: Yoon Hyung‐Jun , Seo Eun Hyun ,   for the Alzheimer’s Disease Neuroimaing Initiative
Published: February 2022

Background

Given that dementia prevalence is getting higher around the world, it is important to make a prognosis about clinical progression after dementia diagnosis. Brain reserve theory suggests that greater reserve supports for functional adaptation to clinical progression in neurodegeneration. Therefore, we examined if reserve proxies at baseline were associated with clinical progression among Alzheimer’s disease dementia (ADD).

Method

We selected ADD data from Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Composite FDG‐PET ROIs (angular gyri, posterior cingulate, and inferior temporal gyri; FDG ROIs), structural MRI volumes for hippocampus, entohinal, and intracranial volume (ICV), American National Adult Reading Test (AMNART) error score, functional activities questionnaire (FAQ), mini mental status examination (MMSE), and other clinical and neuropsychological data, and follow‐up data were downloaded. Clinical progression was measured by change score of clinical dementia rating sum of box (CDR SB change) between baseline and the last follow‐up. Cox proportional hazards models were conducted to investigate the associations between reserve proxies and further progression with covariates of age, gender, and MMSE.

Result

We included 120 patients with ADD at baseline. Mean follow‐up month were 11.42 (5.82, range 6∼24month). Based on CDR SB change, 87 were identified as progression group, while 33 were stable group. At baseline, there were no significant group difference in demographic variables, follow‐up month, CDR SB, FDG ROIs, MRI volumes, distribution of APOE ε4 and Aß positive. However, progression group showed lower performance in AMNART and some neuropsychological tests. Among reserve proxies (education, AMNART, FDG ROIs, ICV, FAQ), FDG ROIs (HR=2.209, p=0.002, 95% CI 1.339‐3.643) was significant in the Cox proportional hazard model. This association was observed only in lager ICV group (HR=4.628, p=0.001, 95% CI 1.810‐11.837), whereas no significant association was found in smaller ICV group.

Conclusion

Our findings indicate that relatively preserved brain metabolism may slow a rate of clinical progression in ADD, particularly in greater ICV group. In addition to ICV, which is widely used proxy for brain reserve, glucose brain metabolism could play a key role in functional compensation in the process of neurodegeneration.
Altered structural connectivity detected with dilated convolutional neural network analysis in the DIAN study and the Wisconsin Registry for Alzheimer’s Prevention
Authors: Zhen Xingjian , Chakraborty Rudrasis , Vogt Nicholas M. , Wang Ruochen , Yang Kao Lee , Adluru Nagesh , Gordon Brian A. , Benzinger Tammie L.S. , McKay Nicole S. , Betthauser Tobey J. , Johnson Sterling C. , Singh Vikas , Bendlin Barbara B. ,   the Dominantly Inherited Alzheimer Network
Published: February 2022

Background

Dominantly inherited Alzheimer’s disease (DIAD) and late onset Alzheimer’s disease (LOAD) are characterized by the accumulation of amyloid pathology, and neurodegeneration which heralds the onset of dementia. Loss of structural connectivity prior to development of dementia may be measured using techniques that are sensitive to subtle neurodegeneration such as diffusion MRI (dMRI). We have previously shown the utility of deep learning (using a dilated convolutional neural network (DCNN) model) for analysis of sequential manifold‐valued data. Here, we apply this approach to dMRI data to test for loss of structural connectivity among mutation carriers who will develop DIAD, as well as among individuals who are at risk for LOAD due to amyloid pathology.

Method

Dataset 1 comprised 170 cognitively unimpaired participants from the Wisconsin Registry for Alzheimer’s Prevention study who underwent [11C]PiB‐PET to determine amyloid status, and dataset 2 comprised 440 participants in the Dominantly Inherited Alzheimer Network (DIAN) study. Demographics are shown in Table 2. Participants underwent diffusion weighted imaging which was processed using MRTrix3 and FSL toolkits. TractSeg was performed on both datasets to generate 50 white matter tracts, and tractometry was performed to generate mean representations of the tracts. Similar to previous work, we trained the dilated CNN model (Figure 1) using DTI values along the tracts for each group. The distance between the parameters of two models is treated as the difference between two groups. We performed permutation testing of 5000 runs on the distance to determine significant group differences within each dataset.

Result

The p‐values for each tract are shown in Table 1. Within the 50 fibers, we identified 14 tracts that differed by amyloid status, and 16 tracts that differed by mutation status. Across the two data sets, 9 tracts, e.g. Arcuate fascicle, and Cingulum, were found to be in common.

Conclusion

We demonstrate the ability to use the dilated CNN model to capture alterations along tract fibers among cognitively unimpaired individuals with preclinical amyloid as well as among mutation carriers who will develop DIAD. Longitudinal studies are needed to determine the temporal relationship between the accumulation of amyloid and neurodegeneration in the development of dementia.
In vivo amyloid staging in individuals with subjective cognitive decline in DELCODE Study
Authors: Levin Fedor , Grothe Michel J. , Dyrba Martin , Boecker Henning , Daamen Marcel , Lange Catharina , Buerger Katharina , Heneka Michael T. , Laske Christoph , Peters Oliver , Priller Josef , Ramirez Alfredo , Schneider Anja , Spottke Annika , Wagner Michael , Düzel Emrah , Jessen Frank , Teipel Stefan J. ,   the DELCODE Study Group
Published: February 2022

Background

In previous research, a data‐driven in vivo staging model of amyloid accumulation was established based on regional frequencies of amyloid positivity in 18F‐florbetapir‐PET scans of cognitively normal older adults. The model was subsequently validated in an independent cohort of participants with subjective memory complaints. In the current study we aim to apply this staging approach in an independent sample of individuals with subjective cognitive decline (SCD) in the multicenter DZNE ‐ Longitudinal Cognitive Impairment and Dementia Study (DELCODE).

Method

PET scans with 18F‐florbetaben were obtained in a group of 63 SCD participants (mean age = 71.84y, range: 60.83‐83y; 35% female) from the DELCODE cohort. Participants also underwent MRI acquisition, clinical and neuropsychological assessments. CSF biomarkers and APOE genotypes were assessed for subsets of participants. In the future analysis we will classify participants into amyloid accumulation stages based on regional amyloid positivity as assessed in PET images.

Result

Among participants with available CSF assessments, 38% had abnormal CSF Aβ42/Aβ40 ratio values indicating amyloid positivity. Frequency of APOE4 allele carriers of 39% was suggestive of APOE4 enrichment.

Conclusion

SCD participants studied within the DELCODE represent a group at an increased risk for preclinical AD. Consistent with that, the current SCD subsample with available 18F‐florbetaben‐PET scans demonstrated heightened rates of abnormal CSF amyloid‐β biomarkers and APOE4 prevalence. Investigation of regional amyloid accumulation in this sample would help assess the validity of the previous in vivo amyloid staging model in preclinical AD, as well as further characterize SCD. In the future analysis we will apply the previously established amyloid staging approach. We will additionally evaluate the hypothesized links between amyloid accumulation stages, cognitive performance, CSF biomarkers and prevalence of APOE genotypes.
Atrophy in bvFTD spans multiple large‐scale networks in prefrontal and temporal cortex
Authors: Eldaief Mark C , Brickhouse Michael , Katsumi Yuta , Carvalho Nicole , Rosen Howard J. , Touroutoglou Alexandra , Dickerson Brad C.
Published: February 2022

Background

Converging evidence suggests that neurodegenerative disorders preferentially affect specific large‐scale neural networks 1. This is thought to explain common phenotypic presentations of these conditions. For example, atrophy patterns in Alzheimer’s disease target episodic memory circuits2. Examination of network‐specific neurodegeneration could lend insight into how these conditions spread within vulnerable cortical systems 3. Behavioral variant Frontotemporal Dementia (bvFTD) is most commonly linked to degeneration in the salience network, with clinical presentations of bvFTD explained as deficits in salience processing 4,5. However, phenotypic presentations of bvFTD are diverse6 and this syndrome is caused by varied proteinopathies and gene mutations7. As such, we hypothesized that bvFTD patients would exhibit atrophy patterns that cross canonical network boundaries within prefrontal and temporal cortex.

Method

We estimated cortical thickness using surface‐based analyses described in our previous studies2 in two independent sporadic bvFTD samples: a Massachusetts General Hospital sample (n=30) and a sample derived from the Frontotemporal Lobar Degeneration Neuroimaging Initiative (NIFD) (n=60; excluding cases contributed by MGH). Cortical thickness in these samples were then compared to that measured in two groups of age and gender matched controls (n=71 and n=133, respectively). In order to estimate individual network atrophy in bvFTD, we then compared the resultant cortical thickness maps to the topography of seven large‐scale cortical networks derived from the Yeo et al. 2011 parcellation8.

Result

We found highly similar patterns of cortical atrophy across the two independent samples. In both samples, cortical atrophy in bvFTD was not confined to the salience network, but also spanned rostral portions of the default‐mode network (including the hippocampal formation), the limbic (semantic appraisal) network, and rostral nodes of the frontoparietal control network. Moreover, regions exhibiting the most prominent atrophy included anterior temporal regions, not only the salience network.

Conclusion

These findings argue against the hypothesis that bvFTD preferentially affects the salience network and instead underscores the distributed impact this syndrome has across prefrontal and anterior temporal cortical circuits. This heterogeneity could reflect the diverse neuropathological etiologies giving rise to the cognitive‐behavioral syndrome of bvFTD. Future efforts should be directed toward examining selectively‐vulnerable circuits in bvFTD syndromes associated with specific molecular pathologies.
Current status and quantitative results of the AMYPAD prognostic and natural history study
Authors: Gispert Juan Domingo , Alves Isadora Lopes , Gray Katherine R. , Buckley Christopher , Collij Lyduine E. , Heeman Fiona , Salvadó Gemma , García David Vállez , Connelly Peter , Boutoleau‐Bretonnière Claire , Pasquier Florence , Dumurgier Julien , Gabelle Audrey , Dubois Bruno , Payoux Pierre , Grau‐Rivera Oriol , Martinez‐Lage Pablo , Boada Mercè , Marquié Marta , Vandenberghe Rik , Hanseeuw Bernard J. , Kivipelto Miia , Schöll Michael , Scheltens Philip , Frisoni Giovanni B. , Ritchie Craig W. , Vellas Bruno , Stephens Andrew W. , Ford Lisa , Molinuevo Jose , Visser Pieter Jelle , Farrar Gill , Barkhof Frederik ,   AMYPAD Consortium
Published: February 2022

Background

Understanding the role of amyloid imaging in the earliest stages of Alzheimer’s Disease (AD) becomes increasingly relevant for secondary prevention. In this context, the AMYPAD Prognostic and Natural History Study (PNHS) is an open‐label, prospective, multi‐centre cohort study (http://amypad.eu/) to determine the value of quantitative amyloid PET imaging in determining AD dementia risk. The study recruits from several European cohorts and aims at enrolling 2000 non‐demented individuals with a particular focus on those with emerging amyloid pathology.

Method

As of January 25th, 2020, AMYPAD PNHS had 17 actively recruiting sites across Europe, and 782 non‐demented participants (>95% cognitively unimpaired) had consented to participate in the study. Of those, 448 are from EPAD LCS, 129 from EMIF‐AD Twin 60++, 111 from FACEHBI, 70 from ALFA+, 17 from FPACK, and 7 from the UCL‐2010‐412 cohort. Of the consented subjects, 334 already had an amyloid PET scan before this study. Within AMYPAD PNHS, 588 subjects have hitherto been scanned with either [18F]flutemetamol or [18F]florbetaben. Of note, 53.6% of the total number of scans have been acquired with a dual‐time window dynamic protocol. The primary outcome measure is the Centiloid value (CL) using the whole cerebellum as reference region, to enable quantitative comparability between the two tracers in the study. Also, images have been visually assessed by local raters. Of the 588 acquired scans, 296 have been quantified with IXICO’s LEAP pipeline and passed Quality Control, thus rendering valid CL values. Subjects were categorized as amyloid‐negative (CL≤12); as in a “gray‐zone” (1250) and a Gaussian Mixture Model was used to assess the population’s Centiloid distribution.

Result

Based on visual assessment, 28% of the fully 296 quantified scans were visually rated as positive and 72% as negative. Quantitatively, 50% of them were categorized as negative, 33% in the gray‐zone, and 17% were positive (Figure 1). Centiloid values ranged from ‐30.3 to 154.2 (Mean±SD: 22.5±32.0 CL) (Figure 2).

Conclusion

Preliminary quantitative results indicate that PNHS is being successful in recruiting a cohort mostly composed of cognitively unimpaired individuals who are enriched for early amyloid abnormalities, which is the intended target population.
Microglial activation and tau propagate jointly across Braak stages
Authors: Pascoal Tharick A. , Benedet Andréa Lessa , Ashton Nicholas J. , Kang Min Su , Therriault Joseph , Chamoun Mira , Lussier Firoza Z. , Tissot Cécile , Ottoy Julie , Mathotaarachchi Sulanta , Stevenson Jenna , Massarweh Gassan , Schöll Michael , Soucy Jean‐Paul , Blennow Kaj , Zetterberg Henrik , Gauthier Serge , Rosa‐Neto Pedro
Published: February 2022

Background

Compelling experimental evidence suggests that microglial activation is involved in the spread of tau neurofibrillary tangles over the neocortex in Alzheimer’s disease (AD). Here, we tested the hypothesis that the spatial propagation of microglial activation and tau accumulation colocalize in a Braak‐like pattern in the human brain.

Method

We studied 130 subjects (86 cognitively unimpaired and 44 cognitively impairment elderly) with microglia activation [11C]PBR28 PET, Amyloid [18F]NAV4694 PET, cognitive tests, magnetic resonance imaging, and cerebrospinal fluid (CSF) biomarkers. Participants also had baseline and follow‐up tau [18F]MK6240 PET scans. We used linear regressions and partial correlations to estimate the association between topographical distributions of microglial activation and tau accumulation.

Result

(A)Microglial activation (MA) connectivity analysis between regions comprising Braak histopathological stages (Braak I‐VI) across our population demonstrated that MA regions correlated hierarchically with each other, where a Braak‐like stage region only correlates with the previous and subsequent stage. (B)Tau tangles connectivity analysis between regions that comprise Braak stages (Braak I‐VI) across our population demonstrated that tau regions correlated hierarchically with each other, where a Braak stage only correlates with the previous/subsequent stage (C)The scatterplot shows that the elements of the MA‐MA matrix and tau‐tau matrix were highly positively correlated with each other, reinforcing the notion of a joint topographic propagation of MA and tau tangles through Braak stages. (D) Rates of tau propagation over 1‐year hierarchically correlated in Braak stages. (E)Significant Pearson correlation between longitudinal tau propagation and baseline tau network. (F)Significant Pearson correlation between longitudinal tau propagation and baseline microglia network. (G)Partial residuals plots show the results of regression between network of tau propagation over 1‐year and both baseline topographic circuits, MA‐MA and tau‐tau networks. The model suggests that the pathways of longitudinal tau propagation depended on underlying microglia, rather than tau circuits. (H)The figure shows thatmicroglial activation levels in the transentorhinal cortex predicted longitudinal tau spread over the neocortex.

Conclusion

Our results support a model in which an interaction between amyloid load and activated microglia set the pace for tau spread across Braak stages, while the simultaneous cerebral presence of these pathologies potentiates the development of dementia.
The heterogeneous brain: Mapping individualised patterns of atrophy in Alzheimer’s disease using spatial normative models
Authors: Verdi Serena , Kia Seyed Mostafa , Marquand Andre F. , Schott Jonathan M. , Cole James H. ,   Alzheimer’s Disease Neuroimaging Initiative
Published: February 2022

Background

Alzheimer’s Disease (AD) is highly heterogeneous, with marked individual differences in clinical presentation and neurobiology. Neuroimaging biomarkers have considerable utility in AD research, however, common statistical designs do not capture neuroanatomical heterogeneity, generally assuming the effects of AD on the brain will be the same in different patients. Spatial normative modelling is an emerging technique that can reveal individual patterns of neuroanatomy by quantifying deviations from normative ranges (Verdi et al., 2021). On multi‐site Alzheimer’s Disease Neuroimaging Initiative (ADNI) data, we applied a hierarchical Bayesian regression (HBR) spatial normative model (Kia et al., 2020). We compared patterns of cortical thickness heterogeneity in AD patients, people with Mild Cognitive Impairment (MCI), and Cognitively Normal (CN) people.

Method

Structural imaging data provided estimates of cortical thickness across 148 (ROIs), generated using FreeSurfer on n=563 T1‐weighted MRI scans acquired across 38 sites. We then applied the HBR spatial normative model, using a separate healthy reference dataset of n=33,073 to index population variability, predicting cortical thickness at each ROI using age and sex. Next, we applied transfer learning, to recalibrate the normative model to the CN participants from ADNI. This generated cortical thickness z‐scores across ROIs for each participant (Fig. 1). Z‐scores < ‐1.96 were identified as outliers.

Result

Linear regression revealed group differences of outliers summed across 148 ROIs: AD had significantly more ROI outliers than MCI and CN participants (β=10.99,95%CI=[5.55,16.42], p=8.28×10‐5) (Fig. 2). ANOVAs at each ROI demonstrated that this difference was within temporal regions (Fig. 3), e.g., parahippocampal gyrus (F(2,23.33),CI=[ 0.29, 0.57],FDR p=3.60×10‐8). Calculating the percentage of outliers in each ROI within groups revealed that outlying ROIs in AD patients only partially overlap. The parahippocampal gyrus had the highest number of AD patients with outliers (n=27 out of n=59 (45.7%)); more than half of the AD group appeared normal in this region (Fig. 4).

Conclusion

Our novel quantitative estimate of spatial heterogeneity of cortical thickness in AD patients suggests that the impact of AD on the brain is not consistent between patients. Individualised patient neuroanatomical maps have the potential to be a marker of disease, and could be used to track an individual’s disease progression or treatment response.
Mild behavioral impairment is associated with progression to Alzheimer's disease: A clinicopathological study
Authors: Ruthirakuhan Myuri , Ismail Zahinoor , Herrmann Nathan , Gallagher Damien , Lanctôt Krista L.
Published: February 2022

Introduction

Mild behavioral impairment (MBI) is characterized by later‐life emergence of neuropsychiatric symptoms. Investigating its relationship with progression to Alzheimer's disease (AD) would provide insight on its importance as a predictor of AD.

Methods

Cognitively normal participants (N = 11,372) from the National Alzheimer's Coordinating Center were stratified by MBI status, using the Neuropsychiatric Inventory‐Questionnaire. We investigated whether MBI and its domains were predictors of progression to clinically‐diagnosed AD. MBI as a predictor of progression to neuropathology‐confirmed AD was also investigated in those with neuropathological data.

Results

Six percent (N = 671) of participants progressed to AD. MBI (N = 2765) was a significant predictor of progression to clinically‐diagnosed (hazard ratio [HR] = 1.75) and neuropathology‐confirmed AD (HR = 1.59). MBI domains were also associated with clinically‐diagnosed AD, with psychosis having the greatest effect (HR = 6.49).

Discussion

These findings support the biological underpinnings of MBI, emphasizing the importance of later life behavioral changes in dementia detection and prognostication.
Cerebrospinal fluid neurofilament light chain differentiates primary psychiatric disorders from rapidly progressive, Alzheimer's disease and frontotemporal disorders in clinical settings
Authors: Eratne Dhamidhu , Loi Samantha M. , Li Qiao‐Xin , Stehmann Christiane , Malpas Charles B. , Santillo Alexander , Janelidze Shorena , Cadwallader Claire , Walia Nirbaanjot , Ney Blair , Lewis Victoria , Senesi Matteo , Fowler Christopher , McGlade Amelia , Varghese Shiji , Ravanfar Parsa , Kelso Wendy , Farrand Sarah , Keem Michael , Kang Matthew , Goh Anita M.Y. , Dhiman Kunal , Gupta Veer , Watson Rosie , Yassi Nawaf , Kaylor‐Hughes Cath , Kanaan Richard , Perucca Piero , Dobson Hannah , Vivash Lucy , Ali Rashida , O'Brien Terence J. , Hansson Oskar , Zetterberg Henrik , Blennow Kaj , Walterfang Mark , Masters Colin L. , Berkovic Samuel F. , Collins Steven , Velakoulis Dennis ,   The MiND Study Group
Published: February 2022

Introduction

Many patients with cognitive and neuropsychiatric symptoms face diagnostic delay and misdiagnosis. We investigated whether cerebrospinal fluid (CSF) neurofilament light (NfL) and total‐tau (t‐tau) could assist in the clinical scenario of differentiating neurodegenerative (ND) from psychiatric disorders (PSY), and rapidly progressive disorders.

Methods

Biomarkers were examined in patients from specialist services (ND and PSY) and a national Creutzfeldt‐Jakob registry (Creutzfeldt‐Jakob disease [CJD] and rapidly progressive dementias/atypically rapid variants of common ND, RapidND).

Results

A total of 498 participants were included: 197 ND, 67 PSY, 161 CJD, 48 RapidND, and 20 controls. NfL was elevated in ND compared to PSY and controls, with highest levels in CJD and RapidND. NfL distinguished ND from PSY with 95%/78% positive/negative predictive value, 92%/87% sensitivity/specificity, 91% accuracy. NfL outperformed t‐tau in most real‐life clinical diagnostic dilemma scenarios, except distinguishing CJD from RapidND.

Discussion

We demonstrated strong generalizable evidence for the diagnostic utility of CSF NfL in differentiating ND from psychiatric disorders, with high accuracy.
Ovariectomized rat model and shape variation in the bony labyrinth
Authors: Ward Devin L. , Schroeder Lauren , Tinius Alexander , Niccoli Sarah , Voth Riley , Lees Simon J. , Silcox Mary , Viola Bence , Sanzo Paolo
Published: February 2022

Postmenopausal osteoporosis is a serious concern in aging individuals, but has not been explored for its potential to alter the shape of the inner ear by way of increased remodeling in the otic capsule. The otic capsule, or bony labyrinth, is thought to experience uniquely limited remodeling after development due to high levels of osteoprotegerin. On this basis, despite the widespread remodeling that accompanies osteoporosis, we hypothesize that both the shape and volume of the semicircular canals will resist such changes. To test this hypothesis, we conducted three‐dimensional geometric morphometric shape analysis on microcomputed tomographic data collected on the semicircular canals of an ovariectomized (OVX) rat model. A Procrustes ANOVA found no statistically significant differences in shape between surgery and sham groups, and morphological disparity testing likewise found no differences in shape variation. Univariate testing found no differences in semicircular volume between OVX and control groups. The range of variation in the OVX group, however, is greater than in the sham group but this difference does not reach statistical significance, perhaps because of a combination of small effect size and low sample size. This finding suggests that labyrinthine shape remains a tool for assessing phylogeny and function in the fossil record, but that it is possible that osteoporosis may be contributing to intraspecific shape variation in the bony labyrinth. This effect warrants further exploration at a microstructural level with continued focus on variables related to remodeling.
Anwendungsmöglichkeiten der neuen „Muster‐Holzbaurichtlinie” für Holzrahmenbauteile
Authors: Scheidel Sabine , Dienst Sebastian , Kornadt Oliver
Published: February 2022

In der Baubranche, wie auch in vielen anderen Bereichen, legen Politik und Gesellschaft immer stärkere Priorität auf ein nachhaltiges, ressourcenschonendes und ökologisches Denken und Handeln. Zur Errichtung und Erweiterung von Gebäuden ist Holz hier als besonders geeignet zu sehen, was auch die Charta für Holz verdeutlicht. Im Juni dieses Jahres wurde die neue Muster‐Richtlinie über brandschutztechnische Anforderungen an Bauteile und Außenwandbekleidungen in Holzbauweise (MHolzBauR) durch die Aufnahme in die Muster‐Verwaltungsvorschrift Technische Baubestimmungen (MVV TB) eingeführt. Bereits vor der offiziellen Einführung wurde diese als ein weiterer Schritt in Richtung der bauaufsichtlich geregelten Holzgebäude bis zur Gebäudeklasse 5 gewertet. Die Richtlinie soll die Anwendung von Holz als Baustoff über eine Geschosshöhe von 13 m hinaus zulässig machen und auch eine Ausführung tragender und raumabschließender Bauteile mit einer feuerbeständigen Anforderung in Holzbauweise ermöglichen. Bei einem Vergleich der neuen MHolzBauR mit der bisher gültigen Muster‐Richtlinie erkennt man jedoch keinen nennenswerten Unterschied zwischen den brandschutztechnischen Anforderungen an eine Holzrahmenkonstruktion. Damit können die lang ersehnten Möglichkeiten für Holzgebäude bis zur Hochhausgrenze nur in Massivholzbauweise realisiert werden. Ein nicht unerheblicher Bereich des Holzbaus bleibt weiterhin auf die Gebäudeklasse 4 begrenzt.
Childhood cancer risk in offspring of parents occupationally exposed to dusts: A register‐based nested case‐control study from Sweden of 5 decades
Authors: Rossides Marios , Kampitsi Christina‐Evmorfia , Talbäck Mats , Wiebert Pernilla , Feychting Maria , Tettamanti Giorgio
Published: February 2022

Background

Some largely inconsistent associations between parental occupational dust exposure and childhood cancer have been reported, with maternal exposures inadequately studied. The authors examined whether maternal or paternal occupational exposure to animal, wood, textile, or paper dust around a child's birth was associated with an increased risk of childhood cancer, both overall and by type (leukemias, lymphomas, central nervous system tumors, and other cancers).

Methods

In this nationwide, register‐based, case‐control study, children who were diagnosed with cancer from 1960 to 2015 were compared with up to 25 matched controls regarding maternal and paternal occupational dust exposure (9653 cases in maternal analyses and 12,521 cases in paternal analyses). Exposures were assessed using a job‐exposure matrix and occupational information from census and register data. By using conditional logistic regression models, adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated.

Results

Neither maternal nor paternal occupational exposure to animal, wood, textile, or paper dust was associated with childhood cancer overall, leukemias, or central nervous system tumors. Maternal, but not paternal, wood dust exposure was associated with an increased risk of lymphoma (OR, 1.42; 95% CI, 1.10‐1.84), particularly non‐Hodgkin lymphoma (OR, 2.03; 95% CI, 1.21‐3.40).

Conclusions

The current study did not confirm the associations reported previously but is the first to suggest a link between maternal occupational exposure to wood dust around pregnancy and lymphoma in the offspring.
Mindfulness‐based and mindfulness‐informed interventions in bipolar disorder: A meta‐analysis based on Becker's method
Authors: Burgos‐Julián Francisco A. , Ruiz‐Íñiguez Raquel , Peña‐Ibáñez Fernando , Montero Ana Carralero , Santed‐Germán Miguel Angel
Published: February 2022

Bipolar disorder is a highly disruptive and debilitating problem. Mindfulness‐based and mindfulness‐informed interventions have exponentially emerged as third‐generation therapies, applied to a wide spectrum of disorders, including bipolar disorder. However, the reviews and meta‐analyses published to date are limited in their conclusions, as they are based on single‐group pretest–posttest cohort designs and mostly focused on mindfulness‐based interventions. The present review and meta‐analysis try to address these limitations, including studies on informed mindfulness, controlled and single‐group designs. It used a specific meta‐analytical procedure that allows an imputation procedure in those designs lacking a comparison group, by means of separate omnibus tests for the experimental and control group. A total of 13 studies (N = 331) were selected. The results showed an absence of effects on depression (g = 0.21) and mania (g = −0.13), but significant moderate effect on anxiety (g = 0.53). In conclusion, both mindfulness interventions showed robust evidence on anxiety symptoms in pretest–posttest periods compared to control groups. Few studies and lack of evidence of follow‐up periods were the main limitations found.
Performance of a Lever‐Gear Type Piezoelectric Energy Harvester for Collecting Pedestrian Energy
Authors: Cai Yuan , Liao Peng , Ma Wenyong , Fu Jiyang , He Yuncheng
Published: February 2022

As pedestrian‐induced energy exists widely in our daily life, the collection of pedestrian energy has attracted increasing attention. Herein, a novel energy harvester is developed to capture the kinetic energy of pedestrians. The mechanical part of the energy harvester mainly consists of a lever structure and a gear transmission component, which is used to convert the kinetic energy of pedestrians into that associated with the rotation of the device. Energy is collected by a polyvinylidene fluoride (PVDF) piezoelectric film. The performance of the harvester is tested under both indoor and outdoor conditions. Experimental results show that the maximum output voltage of the harvester with a single PVDF film is 1170 mV, and the harvester reaches the best output state when the load is 510 kΩ (acceleration 0.3 g (1 g = 9.8 m s−2), frequency 5 Hz) with the maximum output power equal to 1.41 μW. The harvester is then optimized by adding more PVDF films, and the improved device is found to possess a higher working efficiency, with the output voltage and power increased by 58.6% and 26%, respectively. Finally, outdoor tests are conducted, and the results further confirm the feasibility of using the device to harvest the ultralow frequency kinetic energy of pedestrians.
Coordination of mode switching control and SMES unit for low‐voltage ride‐through fulfillment of power electronic transformer
Authors: Chen Lei , Qiao Xuefeng , Zhao Zekai , Wang Xuechun , Chen Hongkun , Li Yanhong , Islam Md. Rabiul , Deng Xinyi , Li Guocheng
Published: February 2022

Power electronic transformer (PET) should have a satisfying low‐voltage ride‐through (LVRT) ability to cope with different kinds and severities of voltage sags. To solve the LVRT issue, this paper proposes to coordinate mode switching control (MSC) and superconducting magnetic energy storage (SMES), and it is to realize the targets of promoting voltage recovery, keeping DC‐link stabilization, and alleviating current inrush. First, the theoretical modeling of a PET incorporating with a SMES unit is implemented, and the PET’s fault transient characterizes as well as the SMES’s potential supportability is analyzed. Then, the coordination philosophy of the MSC and the SMES is presented. For that the voltage sag reaches a certain threshold, the MSC is enabled to remove the PET’s normal control, and the SMES collaboratively operates to lower the DC‐link overvoltage, while avoiding the PET damage. In the process of the coordination control handling the voltage transients, a proper reactive current injection is carried out at the PET’s output stage to assist the voltage recovery, and the PET can possess a better LVRT margin. Using MATLAB, a 3 MW PET with an 8 H/1.2 MJ SMES unit is modeled, and different voltage sag scenarios and utilization ways of the MSC and the SMES are simulated. The comparative analysis results show that the proposed approach realizes a satisfying LVRT for the PET.
Central nervous system organoids for modeling neurodegenerative diseases
Authors: Hou Pei‐Shan , Kuo Hung‐Chih
Published: February 2022

Recent advances in induced pluripotent stem cell (iPSC) technology have allowed researchers to generate neurodegenerative disease‐specific iPSCs and use the cells to derive a variety of relevant cell populations for laboratory modeling and drug testing. Nevertheless, these efforts have faced challenges related to immaturity and lack of complex developmental niches in the derived cell populations, limiting the utility of these in vitro models of neurodegenerative disease. Such limitations may be overcome by using human iPSC technology to generate three‐dimensional (3D) brain organoids, which better recapitulate in vivo tissue architecture than traditional neuronal cultures to provide more complex and representative disease models and drug testing systems. In this review, we focus on the application of pluripotent stem cell‐derived central nervous system (CNS) organoids to model neurodegenerative diseases. We first summarize recent progress in generating and characterizing various CNS organoids from pluripotent stem cells. We then review the application of CNS organoids for modeling several different human neurodegenerative diseases. We also describe several novel pathological mechanisms and drugs that were studied using patient iPSC‐derived CNS organoids. Finally, we discuss remaining challenges and emerging opportunities for the use of 3D brain organoids for in vitro modeling of CNS development and neurodegeneration.
Predictive value of NLR and PLR in missed miscarriage
Authors: Liu Dan , Huang Xinyan , Xu Zhengxian , Chen Minzhi , Wu Manyu
Published: February 2022

Background

The aim of the study was to investigate the predictive value of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in missed miscarriage.

Methods

In this retrospective cohort study, a total of 400 women (involving 200 with missed early miscarriage and 200 with normal pregnancy but terminate by artificial abortion) were included. General clinical data and complete blood count (CBC) such as white blood cells (WBC), red blood cells (RBC), platelet (PLT), red blood cell distribution width‐standard deviation (RDW‐SD), platelet distribution width (PDW), mean platelet volume (MPV), neutrophil count, and lymphocyte count were collected, and the NLR and PLR were calculated for both groups. Receiver operating characteristic curve (ROC) was used to calculate the predictive value.

Results

There was no significant difference in the WBC, RBC, PLT, RDW‐SD, PDW, neutrophil, lymphocyte, NLR, and PLR between the two groups (p > 0.05).But MPV was lower in the missed early miscarriage group than in the control group (p < 0.05), and the area under the working curve (AUC) of ROC was 0.58, specificity and sensitivity was 69% and 47%, respectively.

Conclusion

NLR and PLR were not the suitable indictor for missed miscarriage, but MPV should be a concern in the first trimester.
The impact of storage on extracellular vesicles: A systematic study
Authors: Gelibter Stefano , Marostica Giulia , Mandelli Alessandra , Siciliani Stella , Podini Paola , Finardi Annamaria , Furlan Roberto
Published: February 2022

Mounting evidence suggests that storage has an impact on extracellular vesicles (EVs) properties. While −80°C storage is a widespread approach, some authors proposed improved storage strategies with conflicting results. Here, we designed a systematic study to assess the impact of −80°C storage and freeze‐thaw cycles on EVs. We tested the differences among eight storage strategies and investigated the possible fusion phenomena occurring during storage. EVs were collected from human plasma and murine microglia culture by size exclusion chromatography and ultracentrifugation, respectively. The analysis included: concentration, size and zeta potential (tunable resistive pulse sensing), contaminant protein assessment; flow cytometry for the analysis of two single fluorescent‐tagged EVs populations (GFP and mCherry), mixed before preservation. We found that −80°C storage reduces EVs concentration and sample purity in a time‐dependent manner. Furthermore, it increases the particle size and size variability and modifies EVs zeta potential, with a shift of EVs in size‐charge plots. None of the tested conditions prevented the observed effects. Freeze‐thaw cycles lead to an EVs reduction after the first cycle and to a cycle‐dependent increase in particle size. With flow cytometry, after storage, we observed a significant population of double‐positive EVs (GFP+‐mCherry+). This observation may suggest the occurrence of fusion phenomena during storage. Our findings show a significant impact of storage on EVs samples in terms of particle loss, purity reduction and fusion phenomena leading to artefactual particles. Depending on downstream analyses and experimental settings, EVs should probably be processed from fresh, non‐archival, samples in majority of cases.
Extensive myelitis with eosinophilic meningitis after Chimeric antigen receptor T cells therapy
Authors: Le Calvez Baptiste , Eveillard Marion , Decamps Paul , Aguilar Jesus , Seguin Amélie , Canet Emmanuel , Grain Audrey , Touzeau Cyrille , Tessoulin Benoît , Gastinne Thomas
Published: February 2022

Immune effector cell‐associated neurotoxicity syndrome (ICANS) is a frequent adverse event after Chimeric antigen receptor T cells (CAR‐T cells). A patient treated with anti‐CD19 CAR‐T cells for a refractory mantle cell lymphoma presented at Day 8 post‐infusion with extensive myelitis. Unusual eosinophilia was disclosed in the patient's cerebrospinal fluid. After treatment with methylprednisolone and siltuximab, a decrease in clinical symptoms and magnetic resonance imaging lesions were obtained. This unprecedented presentation of eosinophilic meningitis after CAR‐T cells therapy highlights the need for a better understanding of the physiopathology of ICANS, especially to identify potentially targetable pathways.
Multi‐Crosslinked Hydrogels with Instant Self‐Healing and Tissue Adhesive Properties for Biomedical Applications
Authors: Jiang Yongchao , Li Gaiying , Wang Haonan , Li Qian , Tang Keyong
Published: February 2022

Due to the defects like long gelling time, inferior mechanical properties and weak adhesion, in situ forming hydrogels are still restricted in biomedical applications like viscera rupture and targeted therapy. To address these problems, a new kind of multi‐crosslinked hydrogel (G‐OKG‐DA) consisting of gelatin, oxidized konjac glucomannan (OKG), and dopamine (DA) is proposed in this study. The resulting hybrid hydrogel is endowed with a short gelling time (≈3 min) and injectable capacity. According to the mechanical and adhesive tests, G‐OKG‐DA hydrogel shows a robust tensile strength of 23.94 kPa, as well as a higher adhesive strength (≈150 kPa) than commercial fibrin glue. In addition, an instant self‐healing behavior of G‐OKG‐DA hydrogel can be found, which is attributed to multi‐cross‐linking reactions including Schiff‐based dynamic covalent bonds between OKG and gelatin, oxidative polymerization of DA, and catechol‐mediated chemistry like Michael addition and DA–quinone coupling. Importantly, the multi‐crosslinked hydrogel will not compromise its hemocompatibility and cytocompatibility in vitro, suggesting potential applications in biomedical fields as tissue adhesive and implants.
Effect of KCl deposits in high‐temperature corrosion on chromium‐rich steels in SO2‐containing atmosphere
Authors: Kingsbery Phillip , Stephan‐Scherb Christiane
Published: February 2022

High‐temperature corrosion was studied under multiple chemical loads on ferritic‐austenitic model alloys (Fe–13Cr, Fe–18Cr–12Ni, and Fe‐25Cr–20Ni) with KCl deposit under 0.5% /99.5% Ar gas atmosphere at . Postexposure characterization was done by X‐ray diffraction and scanning electron microscopy. In a pure /Ar environment a protective scale was formed by all samples. The introduction of KCl deposits causes the scale to be nonprotective and multilayered, consisting of CrS, FeS, , and . The impact of the microstructure and alloying elements is discussed.
Recent Progress in Preparation and Application of Fibers Using Microfluidic Spinning Technology
Authors: Zhang Mengfan , Peng Xiaotong , Fan Penghui , Zhou Yingshan , Xiao Pu
Published: February 2022

Microscale fibrous materials with high surface areas and ordered structures have attracted widespread attention recently. Microfluidic spinning technology that can effectively control the sizes, structures, and material compositions of fibers has emerged as a robust approach for the fabrication of high‐performance fibers. In this review, the microfluidic spinning technology used to prepare fibrous materials in terms of preparation principles and geometric configurations is presented. Additionally, several applications of fibers spun by microfluidic spinning technology, especially in tissue engineering, drug release, flexible electronics, water collection, and surgical suturing are introduced. Finally, the current challenges and perspectives of this technology are discussed.
Spatial Adjustment Strategy to Improve the Sensitivity of Ionogels for Flexible Sensors
Authors: Zhang Chao , Yao Miao , Zhao Yingying , Nie Jun , He Yong
Published: February 2022

Recently, ionogels‐based flexible/stretchable sensors have been receiving great attention, which greatly promotes the development of artificial flexible electronics. Except transparency, stretchability, stability, self‐healing, and adhesion, the high conductivity of ionogels and high sensitivity as a sensor still are huge challenges. This work proposes a spatial adjustment strategy to improve sensitivity and conductivity through reducing the spatial hinderance without a change in the compound types and ratio. The addition of space pre‐occupier during the preparation of the ionogel reduces the entanglement of polymer chains for better flowability of the polymer network. After removing the solvent from formed ionogels, the obtained free volume could facilitate the movement of ions and mobility of polymers. Through this way, the sensitivity (up to 1.6 times) and conductivity (up to 1.3 times) of ionogels are successfully improved, while maintaining their excellent transparency, stretchability, stability, and electromechanical properties, such as fast response speed and good repeatability. The detecting ability of movements of different parts of the human body is proved. It is worth mentioning that this simple and effective strategy needs no special requirement for chemical structure, so that it has broad applicability in various systems and opens up a new way for the development of flexible sensors.
Deep Learning‐Based Neuromelanin MRI Changes of Isolated REM Sleep Behavior Disorder
Authors: Gaurav Rahul , Pyatigorskaya Nadya , Biondetti Emma , Valabrègue Romain , Yahia‐Cherif Lydia , Mangone Graziella , Leu‐Semenescu Smaranda , Corvol Jean‐Christophe , Vidailhet Marie , Arnulf Isabelle , Lehéricy Stéphane
Published: February 2022

Background

Isolated REM sleep behavior disorder (iRBD) is considered a prodromal stage of parkinsonism. Neurodegenerative changes in the substantia nigra pars compacta (SNc) in parkinsonism can be detected using neuromelanin‐sensitive MRI.

Objective

To investigate SNc neuromelanin changes in iRBD patients using fully automatic segmentation.

Methods

We included 47 iRBD patients, 134 early Parkinson's disease (PD) patients and 55 healthy volunteers (HVs) scanned at 3 Tesla. SNc regions‐of‐interest were delineated automatically using convolutional neural network. SNc volumes, volumes corrected by total intracranial volume, signal‐to‐noise ratio (SNR) and contrast‐to‐noise ratio were computed. One‐way general linear models (GLM) analysis of covariance (ANCOVA) was conducted while adjusting for age and sex.

Results

All SNc measurements differed significantly between the three groups (except SNR in iRBD). Changes in iRBD were intermediate between those in PD and HVs.

Conclusions

Using fully automated SNc segmentation method and neuromelanin‐sensitive imaging, iRBD patients showed neurodegenerative changes in the SNc at a lower level than in PD patients. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society