bluuebunny/crossref_metadata_2025_split huggingface dataset:
A distributional regression approach to modeling the impact of structural and intermediary social determinants on communities burdened by tuberculosis in Eastern Amazonia – Brazil
Authors: Luciano Giacomet Clóvis , Vieira Ramos Antônio Carlos , Dias Moura Heriederson Sávio , Zamboni Berra Thaís , Alves Yan Mathias , Delpino Felipe Mendes , Farley Jason E. , Reynolds Nancy R. , Alonso Jonas Bodini , Teibo Titilade Kehinde Ayandeyi , Arcêncio Ricardo Alexandre 
Published: November 2022

ABSTRACTBackgroundTB is a disease affected by social determinants of health; however, it is unclear what its structural and intermediary determinants are in Eastern Amazonia. The region contains many natural resources, yet it suffers drastically from poverty, inequality, and neglected diseases. Here, we aimed to employ mathematical modeling to evaluate the influence of structural and intermediary determinants of health on TB in Eastern Amazonia – Brazil.MethodsWe conducted an ecological study. We considered cases diagnosed of TB and collected data by census tract to measure the social determinants. We applied thegeneralized additive model for location, scale, and shape(GAMLSS) framework to identify the effect of social determinants on communities with a high prevalence of TB. The Double Poisson distribution (DPO) was selected and we tested the inclusion of quadratic effects.Results1,730 people were selected. The majority were female (59.3%), aged 31 to 59 years (47.6%), blacks (67.9%), schooling level of 5 to 8 years (18.7%). Prevalence of alcoholism was 8.6% and mental illness 0.7%. The GAMLSS analyses showed that the risk of community incidence of TB is associated with the proportion of the population without basic sanitation and also with the age groups 16-31 years and > 61 years.ConclusionsThe study revealed that GAMLSS is an strategic tool to identify territories at greatest risk for TB. Models should have broader scope to include social determinants so as to better inform policy to reduce inequality and achieving the goal of the End TB strategy.
Shadow imaging for panoptical visualization of living brain tissue
Authors: Dembitskaya Yulia , Boyce Andrew K. J. , Idziak Agata , Langeroudi Atefeh Pourkhalili , Bourdellès Guillaume Le , Girard Jordan , Arizono Misa , Ducros Mathieu , Sato-Fitoussi Marie , de Amezaga Amaia Ochoa , Oizel Kristell , Bancelin Stephane , Mercier Luc , Pfeiffer Thomas , Thompson Roger J. , Kim Sun Kwang , Bikfalvi Andreas , Nägerl U. Valentin 
Published: November 2022

AbstractProgress in neuroscience research hinges on technical advances in visualizing living brain tissue with high fidelity and facility. Current neuroanatomical imaging approaches either require tissue fixation, do not have cellular resolution or only give a fragmented view. Here, we show how regular light microscopy together with fluorescence labeling of the interstitial fluid in the extracellular space provide comprehensive optical access in real-time to the anatomical complexity and dynamics of living brain tissue.
The motor pattern of rolling escape locomotion inDrosophilalarvae
Authors: He Liping , Borjon Lydia , Tracey W. Daniel 
Published: November 2022

SummaryWhen undisturbed,Drosophilalarvae move forward through their environment with sweeping waves of caudal to rostral muscle contraction [1, 2]. In stark contrast, nociceptive sensory stimuli (such as attacks by parasitoid wasps) trigger the larvae to roll across the substrate by corkscrewing around the long body axis [3, 4]. While studies have described the motor pattern of larval crawling [1, 2], the motor pattern of larval rolling escape locomotion remains unknown. Here, we have determined this pattern. To do so, we developed a high speed confocal time-lapse imaging preparation that allowed us to trigger rolling with optogenetics while simultaneously imaging a genetically encoded calcium sensor that was expressed in the muscles. Of the 30 muscles present in each larval abdominal hemisegment we find that only 11 muscles are consistently and specifically activated across segments during rolling. 8 additional muscles are more sparsely activated. Importantly, the sequential pattern of muscle recruitment during rolling is completely distinct from that of forward or reverse crawling. We discover that a roll involves a wave of muscle activation that propagates around the larval circumference (in the transverse plane of each segment) and involves four coactive muscle groups. A pattern of activation progresses from coactive ventral muscle groups to dorsal groups and then spreads across the midline to the contralateral dorsal muscle groups which then progresses back to the ventral groups. Finally, the direction of a roll (either clockwise or counterclockwise around the body) is determined by the clockwise or counterclockwise order of muscle group activation around the transverse plane.
Spatial cell type mapping of multiple sclerosis lesions
Authors: Lerma-Martin Celia , Badia-i-Mompel Pau , Ramirez Flores Ricardo O. , Sekol Patricia , Hofmann Annika , Thäwel Thomas , Riedl Christian J. , Wünnemann Florian , Ibarra-Arellano Miguel A. , Trobisch Tim , Eisele Philipp , Schapiro Denis , Haeussler Maximilian , Hametner Simon , Saez-Rodriguez Julio , Schirmer Lucas 
Published: November 2022

AbstractMultiple sclerosis (MS) is a prototypic chronic-inflammatory disease of the central nervous system. After initial lesion formation during active demyelination, inflammation is gradually compartmentalized and restricted to specific tissue areas such as the lesion rim in chronic-active lesions. However, the cell type-specific and spatially restricted drivers of chronic tissue damage and lesion expansion are not well understood. Here, we investigated the properties of subcortical white matter lesions by creating a cell type-specific spatial map of gene expression across various inflammatory lesion stages in MS. An integrated analysis of single-nucleus and spatial transcriptomics data enabled us to uncover patterns of glial, immune and stromal cell subtype diversity, as well as to identify cell-cell communication and signaling signatures across lesion and non-lesion tissue areas in MS. Our results provide insights into the conversion of the tissue microenvironment from a ‘homeostatic’ to a pathogenic or ‘dysfunctional’ state underlying lesion progression in MS. We expect that this study will help identify spatially resolved cell type-specific biomarkers and therapeutic targets for future interventional trials in MS.
Dodecyl Creatine Ester Improves Cognitive Function and Identifies Drivers of Creatine Deficiency
Authors: Mabondzo Aloïse , Harati Rania , Broca-Brisson Léa , Guyot Anne-Cécile , Costa Narciso , Cacciante Francesco , Putignano Elena , Baroncelli Laura , Skelton Matthew R , Saab Cathy , Martini Emmanuelle , Benech Henri , Joudinaud Thomas , Gaillard Jean-Charles , Armengaud Jean , Hamoudi Rifat A. 
Published: November 2022

AbstractCreatine transporter deficiency prevents creatine uptake into the brain, leading to mental retardation. To better understand the pathophysiology, this study focuses on the identification of biomarkers related to cognitive improvement in a Slc6a8 knockout mouse model (Slc6a8/y) engineered to mimic the clinical features of CTD patients which have low brain creatine content. Shotgun proteomics analysis of 4,035 proteins in four different brain regions; the cerebellum, cortex, hippocampus (associated with cognitive functions) and brain stem, and muscle as a control, was performed in 24 mice. Comparisons of the protein abundance in the four brain regions between DCE-treated intranasally Slc6a8-/y mice and wild type and DCE-treated Slc6a8-/y and vehicle group identified 14 biomarkers, shedding light on the mechanism of action of DCE. Integrative bioinformatics and statistical modeling identified key proteins associated with CTD, including KIF1A and PLCB1. The abundance of these proteins in the four brain regions was significantly correlated with both the object recognition and the Y-maze tests. Functional analysis confirmed their key roles and associated molecules in CTD pathogenesis.
The molecular genetic landscape of human brain size variation
Authors: Seidlitz Jakob , Mallard Travis T. , Vogel Jacob W. , Lee Younga H. , Warrier Varun , Ball Gareth , Hansson Oskar , Hernandez Leanna M. , Mandal Ayan S. , Wagstyl Konrad , Lombardo Michael V. , Courchesne Eric , Glessner Joseph T. , Satterthwaite Theodore D. , Bethlehem Richard A.I. ,   Lifespan Brain Chart Consortium, Tasaki Shinya , Ng Bernard , Gaiteri Chris , Smoller Jordan W. , Ge Tian , Gandal Michael J. , Alexander-Bloch Aaron F. 
Published: November 2022

AbstractHuman brain size increases dynamically through early development, peaks in adolescence, and varies up to two-fold among adults. Although previous studies have elucidated changes in brain size across evolution, development, traits, and diseases, the molecular underpinnings of interindividual variation in brain size remain unknown. Here, we leverage postmortem brain RNA sequencing and estimates of brain weight (BW) in 2,531 individuals across three independent datasets, to identify 928 genes that show genome-wide significant associations with either higher or lower BW (BW+, BW-, respectively). These BW gene sets showed distinct neurodevelopmental trajectories and spatial patterns that mapped onto developmental, functional and cellular axes of brain organization. Expression differences among evolutionarily conserved BW genes were predictive of interspecies differences in brain size, and functional annotation of BW genes revealed enrichment for neurogenesis and cell-cell communication. Genome-wide, transcriptome-wide, and phenome-wide association analyses ofin vivoneuroimaging phenotypes confirmed that the genetic regulation of BW-transcripts influences cortical surface area and volume, as well as behavioral traits related to brain function and disease. Cumulatively, our study represents a major step towards the goal of delineating the causal mechanisms of human brain size variation in health and disease.
Distinct spectral profiles of awake resting EEG in disorders of consciousness - the role of frequency and topography of oscillations
Authors: Drążyk Dominika , Przewrocki Karol , Górska Urszula , Binder Marek 
Published: November 2022

AbstractThe prolonged disorders of consciousness (PDOC) pose a challenge for an accurate clinical diagnosis, mainly due to patients’ scarce or ambiguous behavioral responsiveness. Measurement of brain activity can support better diagnosis, independent of motor restrictions. Methods based on spectral analysis of resting-state EEG appear as a promising path, revealing specific changes within the internal brain dynamics in PDOC patients. In this study we used a robust method of resting-state EEG power spectrum parameter extraction to identify distinct spectral properties for different types of PDOC.Sixty patients and 37 healthy volunteers participated in this study. Patient group consisted of 22 unresponsive wakefulness patients, 25 minimally conscious patients and 13 patients emerging from the minimally conscious state. Ten minutes of resting EEG was acquired during wakefulness and transformed into individual power spectra. For each patient, using the spectral decomposition algorithm, we extracted maximum peak frequency within 1-14 Hz range in the centro-parietal region, and the antero-posterior (AP) gradient of the maximal frequency peak. All patients were behaviorally diagnosed using Coma Recovery Scale - Revised (CRS-R).The maximal peak frequency in the 1-14 Hz range successfully predicted both neurobehavioral capacity of patients as indicated by CRS-R total score and PDOC diagnosis. Additionally in patients in whom only one peak within the 1-14 Hz range was observed, the AP gradient significantly contributed to the accuracy of prediction. We have identified three distinct spectral profiles of patients, likely representing separate neurophysiological modes of thalamocortical functioning. Etiology did not have significant influence on the obtained results.
Evaluation of antibody kinetics and durability in health subjects vaccinated with inactivated COVID-19 vaccine (CoronaVac): A cross-sectional and cohort study in Zhejiang, China
Authors: Zhang Hangjie , Hua Qianhui , Xu Nani , Zhang Xinpei , Chen Bo , Ma Xijun , Hu Jie , Chen Zhongbing , Yu Pengfei , Lei Huijun , Wang Shenyu , Ding Linling , Fu Jian , Liao Yuting , Yang Juan , Jiang Jianmin , Lv Huakun 
Published: November 2022

AbstractBackgroundAlthough inactivated COVID-19 vaccines are proven to be safe and effective in the general population, the dynamic response and duration of antibodies after vaccination in the real world should be further assessed.MethodsWe enrolled 1067 volunteers who had been vaccinated with one or two doses of CoronaVac in Zhejiang Province, China. Another 90 healthy adults without previous vaccinations were recruited and vaccinated with three doses of CoronaVac, 28 days and 6 months apart. Serum samples were collected from multiple timepoints and analyzed for specific IgM/IgG and neutralizing antibodies (NAbs) for immunogenicity evaluation. Antibody responses to the Delta and Omicron variants were measured by pseudovirus-based neutralization tests.ResultsOur results revealed that binding antibody IgM peaked 14–28 days after one dose of CoronaVac, while IgG and NAbs peaked approximately 1 month after the second dose then declined slightly over time. Antibody responses had waned by month 6 after vaccination and became undetectable in the majority of individuals at 12 months. Levels of NAbs to live SARS-CoV-2 were correlated with anti-SARS-CoV-2 IgG and NAbs to pseudovirus, but not IgM. Homologous booster around 6 months after primary vaccination activated anamnestic immunity and raised NAbs 25.5-fold. The NAb inhibition rate subsequently rose to 36.0% for Delta (p=0.03) and 4.3% for Omicron (p=0.004), and the response rate for Omicron rose from 7.9% (7/89) to 17.8% (16/90).ConclusionsTwo doses of CoronaVac vaccine resulted in limited protection over a short duration. The homologous booster slightly increased antibody responses to the Delta and Omicron variants; therefore, the optimization of booster procedures is vital.FundingKey Research and Development Program of Zhejiang Province; Key Program of Health Commission of Zhejiang Province/ Science Foundation of National Health Commission; Major Program of Zhejiang Municipal Natural Science Foundation.
Beta band rhythms influence reaction times
Authors: Rassi Elie , Lin Wy Ming , Zhang Yi , Emmerzaal Jill , Haegens Saskia 
Published: November 2022

AbstractDespite their involvement in many cognitive functions, beta oscillations are among the least understood brain rhythms. Reports on whether the functional role of beta is primarily inhibitory or excitatory have been contradictory. Our framework attempts to reconcile these findings and proposes that several beta rhythms co-exist at different frequencies. Beta frequency shifts and their potential influence on behavior have thus far received little attention. In this magnetoencephalography experiment, we asked whether changes in beta power or frequency in auditory cortex and motor cortex influence behavior (reaction times) during an auditory sweep discrimination task. We found that in motor cortex, increased betapowerslowed down responses, while in auditory cortex, increased betafrequencyslowed down responses. We further characterized beta as transient burst events with distinct spectro-temporal profiles influencing reaction times. Finally, we found that increased motor-to-auditory beta connectivity also slowed down responses. In sum, beta power, frequency, bursting properties, cortical focus, and connectivity profile all influenced behavioral outcomes. Our results imply that the study of beta oscillations requires caution as beta dynamics are multifaceted phenomena, and that several dynamics must be taken into account to reconcile mixed findings in the literature.
Catecholaminergic neuromodulation and selective attention jointly shape perceptual decision-making
Authors: Nuiten Stijn A. , De Gee Jan Willem , Zantvoord Jasper B. , Fahrenfort Johannes J. , van Gaal Simon 
Published: November 2022

SummaryPerceptual decisions about sensory input are influenced by fluctuations in ongoing neural activity, most prominently driven by attention and neuromodulator systems. It is currently unknown if neuromodulator activity and attention differentially modulate perceptual decision-making and/or whether neuromodulatory systems in fact control attentional processes. To investigate the effects of two distinct neuromodulatory systems and spatial attention on perceptual decisions, we pharmacologically elevated cholinergic (through donepezil) and catecholaminergic (through atomoxetine) levels in humans performing a visuo-spatial attention task, while we measured electroencephalography (EEG). Both attention and catecholaminergic enhancement improved decision-making at the behavioral and algorithmic level, as reflected in increased perceptual sensitivity and the modulation of the drift rate parameter derived from drift diffusion modeling. Univariate analyses of EEG data time-locked to the attentional cue, the target stimulus, and the motor response, further revealed that attention and catecholaminergic enhancement both modulated pre-stimulus cortical excitability, cue- and stimulus-evoked sensory activity as well as parietal evidence accumulation signals. Interestingly, we observed both similar, unique, and interactive effects of attention and catecholaminergic neuromodulation on these behavioral, algorithmic, and neural markers of the decision-making process. Thereby, this study reveals an intricate relationship between attentional and catecholaminergic systems and advances our understanding about how these systems jointly shape various stages of perceptual decision-making.
The effect of walking with reduced trunk motion on dynamic stability in healthy adults
Authors: Buurke Tom J.W. , van de Venis Lotte , Keijsers Noël , Nonnekes Jorik 
Published: November 2022

AbstractBackgroundMost people with Parkinson’s Disease (PD) walk with a smaller mediolateral base of support (BoS) compared to healthy people, but the underlying mechanisms remain unknown. According to the extrapolated center of mass (XCoM) concept, a decrease in mediolateral XCoM excursion would require a smaller mediolateral BoS to maintain a constant margin of stability (MoS) and remain stable. As people with PD typically walk with reduced trunk motion, we hypothesized that the mediolateral MoS might stay the same despite a smaller BoS.Research questionAs proof of principle, we assess whether walking with reduced trunk motion results in a smaller step width in healthy adults, without altering the mediolateral MoS.MethodsFifteen healthy adults walked on a treadmill at preferred comfortable walking speed in two conditions. First, the ‘regular walking’ condition without any instructions, and second, the ‘reduced trunk motion’ condition with the instruction: ‘Keep your trunk as still as possible’. Treadmill speed was kept the same in the two conditions. Trunk kinematics, step width, mediolateral XCoM excursion and mediolateral MoS were calculated and compared between the two conditions.ResultsWalking with the instruction to keep the trunk still significantly reduced trunk kinematics. Walking with reduced trunk motion resulted in significant decreases in step width and mediolateral XCoM excursion, but not in the mediolateral MoS. Furthermore, step width and mediolateral XCoM excursion were strongly correlated during both conditions (r=0.887 and r=0.934).SignificanceThis study shows that walking with reduced trunk motion leads to a gait pattern with a smaller BoS in healthy adults, without altering the mediolateral MoS. Our findings indicate a strong coupling between CoM motion state and the mediolateral BoS. We expect that people with PD who walk narrow-based, have a similar mediolateral MoS as healthy people, which will be further investigated.
5-MeO-DMT modifies innate behaviors and promotes structural neural plasticity in mice
Authors: Jefferson Sarah J. , Gregg Ian , Dibbs Mark , Liao Clara , Wu Hao , Davoudian Pasha A. , Sprouse Jeffrey S. , Sherwood Alexander M. , Kaye Alfred P. , Pittenger Christopher , Kwan Alex C. 
Published: November 2022

ABSTRACTSerotonergic psychedelics are gaining increasing interest as potential therapeutics for a range of mental illnesses. Compounds with short-lived subjective effects may be clinically useful because dosing time would be reduced, which may improve patient access. One short-acting psychedelic is 5-MeO-DMT, which has been associated with improvement in depression and anxiety symptoms in early clinical studies. However relatively little is known about the behavioral effects and neural mechanisms of 5-MeO-DMT in animal models. Here we characterized the effects of 5-MeO-DMT on innate behaviors and dendritic architecture in mice. We showed that 5-MeO-DMT induces a dose-dependent increase in head-twitch response that is shorter in duration than that induced by psilocybin at all doses tested. 5-MeO-DMT also substantially suppresses social ultrasonic vocalizations produced during mating behavior. 5-MeO-DMT produces long-lasting increases in dendritic spine density in the mouse medial frontal cortex that are driven by an elevated rate of spine formation. However, unlike psilocybin, 5-MeO-DMT did not affect the size of dendritic spines. These data provide insights into the behavioral and neural consequences underlying the action of 5-MeO-DMT and highlight similarities and differences with those of psilocybin.
Multiple imputation of missing data under missing at random: compatible imputation models are not sufficient to avoid bias
Authors: Curnow Elinor , Carpenter James R , Heron Jon E , Cornish Rosie P , Rach Stefan , Didelez Vanessa , Langeheine Malte , Tilling Kate 
Published: November 2022

AbstractBackgroundEpidemiological studies often have missing data. Multiple imputation (MI) is a commonly-used strategy for such studies. MI guidelines for structuring the imputation model have focused on compatibility with the analysis model, but not on the need for the (compatible) imputation model(s) to be correctly specified. Standard (default) MI procedures use simple linear functions. We examine the bias this causes and performance of methods to identify problematic imputation models, providing practical guidance for researchers.MethodsBy simulation and real data analysis, we investigated how imputation model mis-specification affected MI performance, comparing results with complete records analysis (CRA). We considered scenarios in which imputation model mis-specification occurred because (i) the analysis model was mis-specified, or (ii) the relationship between exposure and confounder was mis-specified.ResultsMis-specification of the relationship between outcome and exposure, or between exposure and confounder in the imputation model for the exposure, could result in substantial bias in CRA and MI estimates (in addition to any bias in the full-data estimate due to analysis model mis-specification). MI by predictive mean matching could mitigate for model mis-specification. Model mis-specification tests were effective in identifying mis-specified relationships. These could be easily applied in any setting in which CRA was, in principle, valid and data were missing at random (MAR).ConclusionWhen using MI methods that assume data are MAR, compatibility between the analysis and imputation models is necessary, but is not sufficient to avoid bias. We propose an easy-to-follow, step-by-step procedure for identifying and correcting mis-specification of imputation models.