bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes to hypothalamic volume and associated subfields during gender-affirming hormone treatment in gender dysphoria
Authors: Konadu ME , Reed MB , Kaufmann U , Handschuh PA , Spies M , Spurny-Dworak B , Klöbl M , Ritter V , Godbersen GM , Seiger R , Baldinger-Melich P , Kranz GS , Lanzenberger R 
Published: February 2022

1.AbstractSex steroid hormones influence hypothalamic micro- and macrostructure in humans and animal models. Neuroimaging studies have suggested that estrogen and anti-androgen treatment decreases volumes of multiple cortical and subcortical brain areas in transgender individuals, including total hypothalamus volume. Here, we aim to further explore potential effects of gender-affirming hormone treatment (GHT) in transgender individuals on hypothalamic volume by providing additional information on hypothalamic subfields.38 transgender men (TM) and 15 transgender women (TW), with gender dysphoria (DSM-5), as well as 32 cisgender women (CW) and 21 cisgender men (CM) underwent two magnetic resonance imaging (MRI) measurements with an interval of at least four months (median interval TM= 134.5 days (interquartile range (IQR): 126-152.25); TW= 149 days (IQR: 126-178.5); CW= 147 days (IQR: 139.75-170.5); CM= 146 days (IQR: 132-247)) between both sessions. In transgender individuals GHT, consisting of estrogen and anti-androgen treatment in TW and testosterone treatment in TM, was initiated directly after the first measurement. To assess how GHT interacts with hypothalamic structures, the hypothalamus and its subunits were segmented using FreeSurfer. Subject group x time interaction effects were evaluated using repeated measures ANCOVA models. The Bonferroni method was used to correct for multiple comparisons.Significant decreases of total hypothalamic volume and associated subunits were detected in TW after estrogen and anti-androgen treatment compared to cisgender groups. Effects were found in the total hypothalamus volume (pcorr= 0.001), the left and right hypothalamus (pcorr= 0.002), the inferior tubular subunit bilaterally (right: pcorr= 0.001; left: pcorr= 0.001), the left superior tubular subunit (pcorr= 0.003) the right anterior inferior subunit (pcorr= 0.002), as well as the right anterior superior subunit (pcorr= 0.0002) of the hypothalamus.Here, we observed significant volumetric effects on the adult human hypothalamus after an interval of at least four months of estrogen and anti-androgen treatment in TW and added knowledge on associated subfields. Further studies investigating influences of sex steroid hormones on brain structure and functional connections are still needed.
Accessing Medical Care for Infertility: A Study of Women in Mexico
Authors: Farland Leslie V. , Khan Sana , Missmer Stacey A. , Stern Dalia , Lopez-Ridaura Ruy , Chavarro Jorge E. , Catzin-Kuhlmann Andres , Sanchez-Serrano Ana Paola , Rice Megan S. , Lajous Martín 
Published: February 2022

AbstractBackgroundInvestigating the burden of access to infertility treatment has primarily been conducted in high-income countries, with little known for low- and middle-income countries, which comprise 80% of the world’s population. The objective of this study was to investigate access to infertility care in Mexico.MethodsThis was a cross-sectional analysis in the Mexican Teachers’ Cohort (MTC), a prospective cohort study of 115,307 Mexican female public school teachers from 12 states in Mexico. Log-binomial models, adjusted for age, hormonal contraceptive use, teaching in a rural school, and speaking an indigenous language, were used to estimate the prevalence ratio (PR) and 95% confidence intervals (95% CI) of accessing medical care for infertility among women reporting a history of infertility.Results19,580 (17%) participants reported a history of infertility. Of those who experienced infertility, 12,470 (63.7%) reported seeking medical care for infertility, among whom 8,467 (67.9%) reported undergoing fertility treatments. Among women who reported a history of infertility, women who taught in a rural school (PR:0.95;0.92-0.97), spoke an indigenous language (PR:0.88; 0.84-0.92), or had less than a university degree (PR:0.93; 0.90-0.97) were less likely to access medical care for fertility. Women who had ever had a mammogram (PR:1.07; 1.05-1.10), had a pap-smear in the past year (PR:1.08;1.06-1.10), or who had utilized private healthcare regularly or in times of illness were more likely to access medical care for fertility.ConclusionUtilization of infertility care varied by demographic and access characteristics, including speaking an indigenous language, teaching in a rural school, and having a private healthcare provider.
Global and local ancestry modulateAPOEassociation with Alzheimer’s neuropathology and cognitive outcomes in an admixed sample
Authors: Naslavsky Michel Satya , Suemoto Claudia K. , Brito Luciano Abreu , Scliar Marília Oliveira , Ferretti-Rebustini Renata Eloah , Rodriguez Roberta Diehl , Leite Renata E. P. , Araujo Nathalia Matta , Borda Victor , Tarazona-Santos Eduardo , Jacob-Filho Wilson , Pasqualucci Carlos , Nitrini Ricardo , Yaffe Kristine , Zatz Mayana , Grinberg Lea T. 
Published: February 2022

AbstractDementia is more prevalent in Blacks than in Whites, likely due to a combination of environmental and biological factors. Paradoxically, clinical studies suggest an attenuation ofAPOEε4 risk of dementia in African ancestry (AFR), but lack of neuropathological data preclude the interpretation of the biological factors underlying these findings, including the association betweenAPOEε4 risk and Alzheimer’s disease (AD) pathology, the most frequent cause of dementia. We investigated the interaction between African ancestry, AD-related neuropathology,APOE genotype, and functional cognition in a postmortem sample of 400 individuals with a range of AD pathology severity and lack of comorbid neuropathology from a cohort of community-dwelling, admixed Brazilians. Increasing proportions of African ancestry (AFR) correlated with a lower burden of neuritic plaques (NP). However, for individuals with high levels of NP and neurofibrillary tangles (NFT), AFR proportion was associated with worse Clinical Dementia Rating sum of boxes (CDR-SOB). AmongAPOEε4 carriers, the association between AFR proportion and CDR-SOB disappeared.APOElocal ancestry inference of a subset of 309 individuals revealed that, inAPOEε4 noncarriers, non-EuropeanAPOEbackground associated with lower NP burden, but with worst cognitive outcomes compared to EuropeanAPOEwhen adjusting by the similar NP burden. Finally,APOEε4 was associated with worse AD neuropathological burden only in a EuropeanAPOEbackground.APOEgenotype and its association with AD neuropathology and clinical pattern are highly influenced by ancestry, with AFR associated with lower NP burden and attenuatedAPOE4risk compared to European ancestry.
PSMA-Hornet: fully-automated, multi-target segmentation of healthy organs in PSMA PET/CT images
Authors: Klyuzhin Ivan S. , Chaussé Guillaume , Bloise Ingrid , Ferres Juan Lavista , Uribe Carlos , Rahmim Arman 
Published: February 2022

ABSTRACTProstate-specific membrane antigen (PSMA) PET imaging represents a valuable source of information reflecting disease stage, response rate, and treatment optimization options, particularly with PSMA radioligand therapy. Quantification of radiopharmaceutical uptake in healthy organs from PSMA images has the potential to minimize toxicity by extrapolation of the radiation dose delivery towards personalization of therapy. Furthermore, factors affecting biodistribution of PSMA radiotracers that remain mostly unknown can be investigated by analyzing PSMA PET images with segmented organs. However, segmentation and quantification of uptake in organs requires labor-intensive organ delineations that are often not feasible in the clinic nor scalable for large clinical trials. In this work we have developed and tested the PSMA Healthy organ segmentation network (PSMA-Hornet), a fully-automated deep neural net for effective and robust segmentation and labelling of 14 healthy organs representing the normal biodistribution of [18F]DCFPyL on PET/CT images.MethodsThe study used manually-segmented [18F]DCFPyL PET/CT images from 100 subjects, and 526 similar images without segmentations. The unsegmented images were used for self-supervised model pretraining. For supervised training, 3-fold cross-validation was used to evaluate the network performance, with 85 subjects reserved for model training, 5 for validation, and 10 for testing. Image segmentation and quantification metrics were evaluated on the test set with respect to manual segmentations by a nuclear medicine physician.ResultsWith our best model, the lowest mean Dice coefficient on the test set was 0.826 for the sublingual gland, and the highest was 0.964 for liver. The highest mean error in tracer uptake quantification was 13.9% in the sublingual gland. Self-supervised pretraining improved training convergence, train-to-test generalization, and segmentation quality. In addition, we found that a multi-target network produced significantly higher segmentation accuracy than single-organ networks.ConclusionThe developed network can be used to automatically obtain high-quality organ segmentations for PSMA image analysis tasks. It can be used to reproducibly extract imaging data, and holds promise for clinical applications such as personalized radiation dosimetry and improved radioligand therapy.
Test-retest reproducibility of human brain multi-slice 1H FID-MRSI data at 9.4 T after optimization of lipid regularization, macromolecular model and spline baseline stiffness
Authors: Ziegs Theresia , Wright Andrew Martin , Henning Anke 
Published: February 2022

Abstract•PurposeThis study analyzes the effects of retrospective lipid suppression, a simulated macromolecular prior knowledge and different spline baseline stiffness values on 9.4 T multi-slice proton FID-MRSI data spanning the whole cerebrum of human brain and its reproducibility of metabolite ratio (/tCr) maps for 10 brain metabolites.•MethodsMeasurements were performed twice on five volunteers using a non-accelerated FID MRSI 2D sequence at 9.4 T. The effects of retrospective lipid L2-regularization, macromolecular spectrum and different LCModel baseline flexibilities on SNR, FWHM, fitting residual, CRLB and the concentration ratio maps were investigated. Intra-subject, inter-session coefficient of variation of the mean metabolite ratios (/tCr) of each slice was calculated.•ResultsL2-regularization provided effective suppression of lipid-artifacts, but should be avoided if no artifacts are detected. Transversal, sagittal and coronal of many metabolite ratio maps correspond to anatomically expected concentration relations in gray and white matter for the majority of the cerebrum when using a flexible baseline in LCModel fit. Additionally, results from the second measurements of the same subjects show that slice positioning and data quality correlate significantly to the first measurement.•ConclusionConcentration ratio maps (/tCr) for 4 metabolites (tCho, NAA, Glu, mI) spanning the majority and six metabolites (NAAG, GABA, GSH, Tau, Gln, Asp) covering 32 mm in the upper part of the brain were acquired at 9.4 T using multi-slice FID MRSI with retrospective lipid suppression, a macromolecular spectrum and a flexible LCModel baseline.
Human orbitofrontal cortex signals decision outcomes to sensory cortex during flexible tactile learning
Authors: Wang Bin A. , Veismann Maike , Banerjee Abhishek , Pleger Burkhard 
Published: February 2022

AbstractThe ability to respond flexibly to an ever-changing environment relies on the orbitofrontal cortex (OFC). How the OFC associates sensory information with predicted outcomes to enable flexible sensory learning in humans remains elusive. Here, we combine a probabilistic tactile reversal learning task with functional magnetic resonance imaging (fMRI) to investigate how lateral OFC (lOFC) interacts with the primary somatosensory cortex (S1) to guide flexible tactile learning in humans. fMRI results reveal that lOFC and S1 exhibit distinct task-dependent engagement: while the lOFC responds transiently to unexpected outcomes immediately following reversals, S1 is persistently engaged during re-learning. Unlike the contralateral stimulus-responsive S1, activity in ipsilateral S1 mirrors the outcomes of behavior during re-learning, which is closely related to top-down signals from lOFC. These findings suggest that lOFC contributes to teaching signals to dynamically update representations in sensory areas, which implements computations critical for adaptive behavior.
A Prism Vote Framework for Individualized Risk Prediction of Traits in Genome-wide Sequencing Data of Multiple Populations
Authors: Xia Xiaoxuan , Sun Rui , Zhang Yexian , Wei Yingying , Li Qi , Chong Marc Ka Chun , Wu William Ka Kei , Zee Benny Chung-Ying , Tang Hua , Wang Maggie Haitian 
Published: February 2022

AbstractMulti-population cohorts offer unprecedented opportunities for profiling disease risk in large samples, however, heterogeneous risk effects underlying complex traits across populations make integrative prediction challenging. In this study, we propose a novel Bayesian probability framework, the Prism Vote (PV), to construct risk predictions in heterogeneous genetic data. The PV views the trait of an individual as a composite risk from subpopulations, in which stratum-specific predictors can be formed in data of more homogeneous genetic structure. Since each individual is represented by a composition of subpopulation memberships, the framework enables individualized risk characterization. Simulations demonstrated that the PV framework applied with alternative prediction methods significantly improved prediction accuracy in mixed and admixed populations. The advantage of PV enlarges as the sample size, genetic heterogeneity, and population diversity increase. In two real genome-wide association data consists of multiple populations, we showed that the framework enhanced prediction accuracy of the linear mixed model by up to 12.1% in five-group cross validations. The proposed framework offers a new aspect to analyze individual’s disease risk and improve accuracy for predicting complex traits in genome data.
Taurine or N-acetylcysteine treatments prevent memory impairment and metabolite profile alterations in the hippocampus of high-fat diet-fed female mice
Authors: Garcia-Serrano Alba M. , Vieira Joao P.P. , Fleischhart Veronika , Duarte João M.N. 
Published: February 2022

AbstractObesity impacts brain metabolism and function, and constitutes a risk factor for dementia development. Long-term exposure to obesogenic diets leads to taurine accumulation in the hippocampus of rodents. Taurine has putative beneficial effects on cell homeostasis, and is reported to improve cognition. Therefore, hippocampal taurine accumulation in obese and diabetic models might constitute a counteracting response to metabolic stress. This study tested the hypothesis that treatment with taurine or with N-acetylcysteine (NAC), which provides cysteine for the synthesis of taurine and the antioxidant glutathione, prevent obesity-associated hippocampal alterations and memory impairment. Female mice were fed either a regular diet or a high-fat diet (HFD). For the same period, some mice had access to 3%(w/v) taurine or 3%(w/v) NAC in the drinking water. After 2 months, magnetic resonance spectroscopy was used to measure metabolite profiles. Then, memory was assessed in novel object and novel location recognition tests. HFD feeding caused memory impairment in both tests, and reduced concentration of lactate, phosphocreatine-to-creatine ratio, and the neuronal marker N-acetylaspartate in the hippocampus. Both taurine and NAC prevented HFD-induced memory impairment and N-acetylaspartate reduction. NAC, but not taurine, prevented the HFD-induced reduction of lactate and phosphocreatine-to-creatine ratio. Analysis of the metabolite profile further revealed prominent NAC/taurine-induced increase of glutamate and GABA levels in the hippocampus. We conclude that NAC and taurine prevent of neuronal dysfunction, while only NAC prevents energy metabolism dysregulation in HFD-induced obesity in female mice.
No evidence that post-training D2R dopaminergic drug administration affects fear generalization in male rats
Authors: Schroyens Natalie , Vercammen Laura , Özcan Burcu , Ossorio Salazar Victoria Aurora , Zaman Jonas , De Bundel Dimitri , Beckers Tom , Luyten Laura 
Published: February 2022

AbstractThe neurotransmitter dopamine plays an important role in the processing of emotional memories, and prior research suggests that dopaminergic manipulations immediately after fear learning can affect the retention and generalization of acquired fear. The current study focuses specifically on the role of dopamine D2 receptors (D2Rs) in adult, male Wistar rats. In a series of five experiments, D2R (ant)agonists were injected systemically immediately after differential cued fear conditioning (CS+ followed by shock, CS− without shock). All five experiments involved the administration of the D2R agonist quinpirole at different doses versus saline (n = 12, 16 or 44 rats/group). Additionally, one of the studies administered the D2R antagonist raclopride (n = 12). One day later, freezing during the CS+ and CS− was assessed. We found no indications for an effect of quinpirole or raclopride on fear generalization during this drug-free test. Importantly, and contradicting prior research in mice, the evidence for the absence of an effect of quinpirole (1 mg/kg) on fear generalization was substantial according to Bayesian analyses and was observed in a highly powered experiment (N = 87). We did find acute behavioral effects in line with the literature, for both quinpirole and raclopride in a locomotor activity test.
Rabbit Hindlimb Kinematics and Ground Contact Pressure During the Stance Phase of Hopping Gait
Authors: Hall Patrick T. , Stubbs Caleb , Anderson David E. , Greenacre Cheryl B. , Crouch Dustin L. 
Published: February 2022

AbstractThough the rabbit is a common animal model in musculoskeletal research, there is very limited data reported on healthy rabbit biomechanics. Our objective was to quantify the normative hindlimb biomechanics of six New Zealand White rabbits (3 male, 3 female) during the stance phase of hopping gait. We measured biomechanics by synchronously recording sagittal plane motion and ground contact pressure using a video camera and pressure mat, respectively. Both foot angle (i.e., angle between foot and ground) and ankle angle curves were unimodal. The peak ankle dorsiflexion angle was 65.9°±12.7° and occurred at 39% stance, while the peak ankle plantarflexion angle was 136.9°±7.8° at toe-off. Minimum and maximum foot angles were 16.6°±6.4° at 12% stance and 125.4°±4.0° at toe-off, respectively. During stance, the knee joint center gradually progressed 4.7 cm downward and 18.1 cm forward, on average. The maximum vertical ground reaction force and contact area, both averaged across rabbits, were 42.5 ± 11.4 %BW and 7.5 ± 1.8 cm2, respectively. Our study confirmed that rabbits exhibit a plantigrade gait pattern, similar to humans. Future studies can reference our data to quantify the extent to which orthopedic interventions affect rabbit biomechanics.
An in vitro model of fibrosis using crosslinked native extracellular matrix-derived hydrogels to modulate biomechanics without changing composition
Authors: Nizamoglu M. , de Hilster R.H.J , Zhao F. , Sharma P.K. , Borghuis T. , Harmsen M.C. , Burgess J.K. 
Published: February 2022

AbstractExtracellular matrix (ECM) is a dynamic network of proteins, proteoglycans and glycosaminoglycans, providing structure to the tissue and biochemical and biomechanical instructions to the resident cells. In fibrosis, the composition and the organization of the ECM are altered, and these changes influence cellular behaviour. Biochemical (i. e. protein composition) and biomechanical changes in ECM take place simultaneously in vivo. Investigating these changes individually in vitro to examine their (patho)physiological effects has been difficult. In this study, we generated an in vitro model to reflect the altered mechanics of a fibrotic microenvironment through applying fibre crosslinking via ruthenium/sodium persulfate crosslinking on native lung ECM-derived hydrogels. Crosslinking of the hydrogels without changing the biochemical composition of the ECM resulted in increased stiffness and decreased viscoelastic stress relaxation. The altered stress relaxation behaviour was explained using a generalized Maxwell model. Fibre analysis of the hydrogels showed that crosslinked hydrogels had a higher percentage of matrix with a high density and a shorter average fibre length. Fibroblasts seeded on ruthenium-crosslinked lung ECM-derived hydrogels showed myofibroblastic differentiation with a loss of spindle-like morphology together with greater α-smooth muscle actin (α-SMA) expression, increased nuclear area and circularity without any decrease in the viability, compared with the fibroblasts seeded on the native lung-derived ECM hydrogels. In summary, ruthenium crosslinking of native ECM-derived hydrogels provides an exciting opportunity to alter the biomechanical properties of the ECM-derived hydrogels while maintaining the protein composition of the ECM to study the influence of mechanics during fibrotic lung diseases.
Residual DNA in enzymes may pose a challenge for DIY RNA sequencing protocols: how to deal
Authors: Krivoy Andrey , Botsmanov Yegor , Cheranev Valery , Shmitko Anna , Belova Vera , Moskalenko Viktoriya , Afasizhev Robert , Shut Anastasia , Korostin Dmitriy , Rebrikov Denis 
Published: February 2022

AbstractHigh-throughput RNA sequencing (RNA-seq) is widely employed for gene expression profiling. This report on do-it-yourself RNA-Seq library preparation pitfalls, highlighting their correct identification and successful overcoming, may be helpful to research groups commencing a DIY RNA-Seq workflow and facing similar problems.
A novel hidden Markov approach to studying dynamic functional connectivity states in human neuroimaging
Authors: Hussain Sana , Langley Jason , Seitz Aaron R. , Hu Xiaoping P. , Peters Megan A. K. 
Published: February 2022

AbstractIntroductionHidden Markov models are a popular choice to extract and examine recurring patterns of activity or functional connectivity in neuroimaging data, both in terms of spatial patterns and their temporal progression. Although many diverse hidden Markov models have been applied to neuroimaging data, most have defined states based on activity levels (intensity-based states) rather than patterns of functional connectivity between brain areas (connectivity-based states), which is problematic if we want to understand connectivity dynamics: intensity-based states are unlikely to provide comprehensive information about dynamic connectivity patterns.MethodsWe addressed this problem by introducing a new hidden Markov model that defines states based on full functional connectivity profiles among brain regions. We empirically explored the behavior of this new model in comparison to existing approaches based on intensity-based or summed functional connectivity states using the HCP unrelated 100 functional magnetic resonance imaging “resting state” dataset.ResultsOur ‘full functional connectivity’ model discovered connectivity states with more distinguishable (i.e., unique and separable from each other) patterns than previous approaches, and recovered simulated connectivity-based states more faithfully than the other models tested.DiscussionThus, if our goal is to extract and interpret connectivity states in neuroimaging data, our new model outperforms previous methods which miss crucial information about the evolution of functional connectivity in the brain.Impact statementHidden Markov models can be used to investigate brain states noninvasively. Previous models “recover” connectivity from intensity-based hidden states, or from connectivity ‘summed’ across nodes. Here we introduce a novel connectivity-based hidden Markov model and show how it can reveal true connectivity hidden states under minimal assumptions.