bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential proliferation regulates multi-tissue morphogenesis during embryonic axial extension: Integrating viscous modeling and experimental approaches
Authors: Romanos Michèle , Salisbury Tasha , Stephan Samuel , Lansford Rusty , Degond Pierre , Trescases Ariane , Bénazéraf Bertrand 
Published: February 2024

AbstractThe study of how mechanical interactions and different cellular behaviors affect tissues and embryo shaping has been and remains an important challenge in biology. Axial extension is a morphogenetic process that results in the acquisition of the elongated shape of the vertebrate embryonic body. Several adjacent tissues are involved in the process, including the tissues that form the spinal cord and musculoskeletal system: the neural tube and the paraxial mesoderm, respectively. Although we have a growing understanding of how each of these tissues elongates, we still need to fully understand the morphogenetic consequences of their growth and mechanical interactions. In this study, we develop a 2D multi-tissue continuum-based mathematical model to simulate and study how differential growth, tissue biophysical properties, and mechanical interactions affect the morphogenesis of the embryonic body during axial extension. Our model captures the long-term dynamics of embryonic posterior tissues previously observedin vivoby time-lapse imaging of bird embryos. It reveals the underestimated influence of differential tissue proliferation rates in inter-tissue interaction and shaping by capturing the relative impact of this process on tissue dynamics. We verified the predictions of our model in quail embryos by showing that decreasing the rate of cell proliferation in the paraxial mesoderm affects long-term tissue dynamics and shaping of both the paraxial mesoderm and the neighboring neural tube. Overall, our work provides a new theoretical platform to consider the long-term consequences of tissue differential growth and mechanical interactions on morphogenesis.
Stimulation mapping and whole-brain modeling reveal gradients of excitability and recurrence in cortical networks
Authors: Momi Davide , Wang Zheng , Parmigiani Sara , Mikulan Ezequiel , Bastiaens Sorenza P. , Oveisi Mohammad P. , Kadak Kevin , Gaglioti Gianluca , Waters Allison C. , Hill Sean , Pigorini Andrea , Keller Corey J. , Griffiths John D. 
Published: February 2024

ABSTRACTThe human brain exhibits a modular and hierarchical structure, spanning low-order sensorimotor to high-order cognitive/affective systems. What is the causal significance of this organization for brain dynamics and information processing properties? We investigated this question using rare simultaneous multimodal electrophysiology (stereotactic and scalp EEG) recordings in patients during presurgical intracerebral electrical stimulation (iES). Our analyses revealed an anatomical gradient of excitability across the cortex, with stronger iES-evoked EEG responses in high-order compared to low-order regions. Mathematical modeling further showed that this variation in excitability levels results from a differential dependence of recurrent feedback from non-stimulated regions across the anatomical hierarchy, and could be extinguished by suppressing those connections in-silico. High-order brain regions/networks thus show a more functionally integrated processing style than low-order ones, which manifests as a spatial gradient of excitability that is emergent from, and causally dependent on, the underlying hierarchical network structure.
Human stem cell derived neurons and astrocytes to detect novel auto-reactive IgG signature in immune-mediated neurological diseases
Authors: Mathias Amandine , Perriot Sylvain , Jones Samuel , Canales Mathieu , Bernard-Valnet Raphael , Gimenez Marie , Torcida Nathan , Oberholster Larise , Hottinger Andreas F. , Zekeridou Anastasia , Theaudin Marie , Pot Caroline , Du Pasquier Renaud 
Published: February 2024

AbstractBackground and objectivesUp to 46% of patients with presumed autoimmune limbic encephalitis are seronegative for all currently known CNS antigens. We developed a cell-based assay (CBA) to screen for novel neural antibodies in serum and CSF using neurons and astrocytes derived from human induced pluripotent stem cells (hiPSC).MethodsHuman iPSC-derived astrocytes or neurons were incubated with serum/CSF from 99 patients (42 with inflammatory neurological diseases (IND) and 57 with non-IND (NIND)). The IND group included 11 patients with previously established neural antibodies, six with seronegative neuromyelitis optica spectrum disorder (NMOSD), 12 with suspected autoimmune encephalitis/paraneoplastic syndrome (AIE/PNS), and 13 with other IND (OIND). IgG binding to fixed CNS cells was detected using fluorescently-labelled antibodies and analyzed through automated fluorescence measures. IgG neuronal/astrocyte reactivity was further analyzed by flow cytometry. Peripheral blood mononuclear cells (PBMC) were used as CNS-irrelevant control target cells. Reactivity profile was defined as positive using a Robust regression and Outlier removal test with a false discovery rate at 10% following each individual readout.ResultsUsing our CBA, we detected antibodies recognizing hiPSC-derived neural cells in 19/99 subjects. Antibodies bound specifically to astrocytes in nine cases, to neurons in eight cases and to both cell types in two cases, as confirmed by microscopy single-cell analyses. Highlighting the significance of our novel 96-well CBA assay, neural-specific antibody binding was more frequent in IND (15/42) than in NIND patients (4/57) (Fisher test,p=0.0005). Three of three patients with astrocyte- reactive (2 AQP4+ NMO, 1 GFAP astrocytopathy), and 3/4 with intracellular neuron-reactive antibodies (2 Hu+, 1 Ri+ AIE/PNS), as identified in diagnostic laboratories, were also positive with our CBA. Most interestingly, we showed antibody-reactivity in 2/6 seronegative NMOSD, 6/12 probable AIE/PNS, and 1/13 OIND. Flow cytometry using hiPSC-derived CNS cells or PBMC detected antibody binding in 13 versus 0 patients, respectively, establishing the specificity of the detected antibodies for neural tissue.DiscussionOur unique hiPSC-based CBA allows for the screening of novel neuron-/astrocyte-reactive antibodies in patients with suspected immune-mediated neurological syndromes, and negative testing in established routine laboratories, opening new perspectives in establishing early diagnosis of such complex diseases.
Minimally invasive serial collection of cerebrospinal fluid reveals sex-dependent differences in neuroinflammation in a rat model of mild traumatic brain injury
Authors: Karam Josh , Ashfaq Nimrah , Benitez Cynthia , Morales Victor , Partida Elizabeth , Hernandez Michelle , Yokoyama Jordan , Villegas Alyssa , Brown Brielle , Sakthivel Pooja , Anderson Aileen J. , Cummings Brian J. 
Published: February 2024

AbstractTraumatic brain injuries (TBI) are the seventh leading cause of disability globally with 48.99 million prevalent cases and 7.08 million years lived with diability. Approximately 80% of TBI patients are diagnosed with mild TBI (mTBI), or concussion, caused by nonpenetrating mechanical trauma to the head or body along with sudden rotational motion of the head. Studies investigating the temporal dynamics of neuroinflammation after mTBI are greatly needed. Without longitudinal studies, translating preclinical studies to clinical studies remains challenging as the difference in timing remains poorly understood. In this study, we describe a method of minimally invasive serial cerebrospinal fluid (CSF) collection that enables longitudinal investigation of CSF inflammation. The method described in this study can easily be adapted by any laboratory prepared for animal studies. Multiplex immunoassay of serially collected and singly collected CSF samples show collection frequency does not alter protein expression in the CSF. Further, sex-dependent differences in TBI have been reported, but remain poorly understood. This study establishes a framework for assessing sex difference in neuroinflammation after a concussion. We showed that results vary based on the framing of the statistical test. However, it is evident that males experience a more robust inflammatory response to a single concussion than females.
Intra-clustering analysis reveals tissue-specific mutational patterns
Authors: Choudalakis Stamatis , Kastis George , Dikaios Nikolaos 
Published: February 2024

AbstractThe identification of tissue-specific mutational patterns associated with cancer development is challenging due to the low frequency of certain mutations and the high variability among tumors within the same cancer type. To address the inter-tumoral heterogeneity issue, our study aims to uncover infrequent mutational patterns by leveraging clustering analysis. To that end, a Network Graph of 8303 patients and 198 genes was constructed from single-point-mutation data that were retrieved from The Cancer Genome Atlas (TCGA). Patient-gene groups were retrieved with the parallel use of two separate methodologies based on the: (a) Barber’s modularity index, and (b) network dynamics. An intra-clustering analysis was employed to explore the patterns within smaller patient subgroups, which involved the Fisher’s exact test, multiple correspondence analysis and DISCOVER. This analysis was applied over 24 statistically meaningful groups of 2619 patients spanning 21 cancer types and it recovered 42 mutational patterns that are not reported in the TCGA consortium analysis publications. Notably, our findings: (i) suggest that AMER1 mutations are a putative separative element between colon and rectal adenocarcinomas, (ii) highlight the significant presence of RAC1 in head and neck squamous cell carcinoma (iii) suggest that EP300 mutations in head and neck squamous cell carcinoma are irrelevant of the HPV status of the patients and (iv) show that mutational-based clusters can contain patients with contrasting genetic alterations.SignificanceThe submitted paper proposes a novel method to identify infrequent cancer-specific mutational patterns through network graphs and clustering analysis.This analysis recovered: (a) 3 statistically significant cancer-gene relations that are not reported in the corresponding TCGA consortium analyses, (b) 28 known cancer-gene relations, (c) 39 significant patterns of co-occurrence or of mutual exclusivity that are not reported in current literature and (d) 14 reported significant mutational patterns.
Emo-FilM: A multimodal dataset for affective neuroscience using naturalistic stimuli
Authors: Morgenroth Elenor , Moia Stefano , Vilaclara Laura , Fournier Raphael , Muszynski Michal , Ploumitsakou Maria , Almató-Bellavista Marina , Vuilleumier Patrik , Van De Ville Dimitri 
Published: February 2024

AbstractThe extensive Emo-FilM dataset stands forEmotion research usingFilms and fMRI in healthy participants. This dataset includes detailed emotion annotations by 44 raters for 14 short films with a combined duration of over 2½ hours, as well as recordings of respiration, heart rate, and functional magnetic resonance imaging (fMRI) from a different sample of 30 individuals watching the same films. The detailed annotations of experienced emotion evaluated 50 items including ratings of discrete emotions and emotion components from the domains of appraisal, motivation, motor expression, physiological response, and feeling. Quality assessment for the behavioural data shows a mean inter-rater agreement of 0.38. The parallel fMRI data was acquired at 3 Tesla in four sessions, accompanied with a high-resolution structural (T1) and resting state fMRI scans for each participant. Physiological recordings during fMRI included heart rate, respiration, and electrodermal activity (EDA). Quality assessment indicators confirm acceptable quality of the MRI data. This dataset is designed, but not limited, to studying the dynamic neural processes involved in emotion experience. A particular strength of this data is the high temporal resolution of behavioural annotations, as well as the inclusion of a validation study in the fMRI sample. This high-quality behavioural data in combination with continuous physiological and MRI measurements makes this dataset a treasure trove for researching human emotion in response to naturalistic stimulation in a multimodal framework.
HB-EGF and EGF infusion following CNS demyelination mitigates age-related decline in regeneration of oligodendrocytes from neural precursor cells originating in the ventricular-subventricular zone
Authors: Moradi Kaveh , Mitew Stanislaw , Xing Yao Lulu , Merson Tobias D. 
Published: February 2024

AbstractIn multiple sclerosis (MS), chronic demyelination initiated by immune-mediated destruction of myelin, leads to axonal damage and neuronal cell death, resulting in a progressive decline in neurological function. The development of interventions that potentiate remyelination could hold promise as a novel treatment strategy for MS. To this end, our group has demonstrated that neural precursor cells (NPCs) residing in the ventricular-subventricular zone (V-SVZ) of the adult mouse brain contribute significantly to remyelination in response to central nervous system (CNS) demyelination and can regenerate myelin of normal thickness. However, aging takes its toll on the regenerative potential of NPCs and reduces their contribution to remyelination. In this study, we investigated how aging influences the contribution of NPCs to oligodendrogenesis during the remyelination process and whether the delivery of growth factors into the brains of aged mice could potentiate the oligodendrogenic potential of NPCs. To enable us to map the fate of NPCs in response to demyelination induced at different postnatal ages,Nestin-CreERT2;Rosa26-LSL-eYFPmice were gavaged with tamoxifen at either 8 weeks, 30 weeks or one year of age before being challenged with cuprizone for a period of six weeks. Using osmotic minipumps, we infused heparin-binding EGF-like growth factor (HB-EGF), and/or epidermal growth factor (EGF) into the cisterna magna for a period of two weeks beginning at the peak of cuprizone-induced demyelination (n=6-8 mice per group). Control mice received artificial cerebrospinal fluid (vehicle) alone. Mice were perfused six weeks after cuprizone withdrawal and the contribution of NPCs to oligodendrocyte regeneration in the corpus callosum was assessed. Our data reveal that although NPC-derived oligodendrocyte generation declined dramatically with age, this decline was partially reversed by growth factor infusion. Notably, co-infusion of EGF and HB-EGF increased oligodendrocyte regeneration twofold in some regions of the corpus callosum. Our results shed light on the beneficial effects of EGF and HB-EGF for increasing the contribution of NPCs to remyelination and indicate their therapeutic potential to combat the negative effects of aging upon remyelination efficacy.
The choice-wide behavioral association study: data-driven identification of interpretable behavioral components
Authors: Kastner David B. , Williams Greer , Holobetz Cristofer , Romano Joseph P. , Dayan Peter 
Published: February 2024

AbstractBehavior contains rich structure across many timescales, but there is a dearth of methods to identify relevant components, especially over the longer periods required for learning and decision-making. Inspired by the goals and techniques of genome-wide association studies, we present a data-driven method—the choice-wide behavioral association study: CBAS—that systematically identifies such behavioral features. CBAS uses a powerful, resampling-based, method of multiple comparisons correction to identify sequences of actions or choices that either differ significantly between groups or significantly correlate with a covariate of interest. We apply CBAS to different tasks and species (flies, rats, and humans) and find, in all instances, that it provides interpretable information about each behavioral task.
Neurons underlying aggressive actions that are shared by both males and females inDrosophila
Authors: Tao Liangyu , Ayembem Deven , Barranca Victor J. , Bhandawat Vikas 
Published: February 2024

AbstractAggression involves both sexually monomorphic and dimorphic actions. How the brain implements these two types of actions is poorly understood. We found that a set of neurons, which we call CL062, previously shown to mediate male aggression also mediate female aggression. These neurons elicit aggression acutely and without the presence of a target. Although the same set of actions is elicited in males and females, the overall behavior is sexually dimorphic. The CL062 neurons do not expressfruitless, a gene required for sexual dimorphism in flies, and expressed by most other neurons important for controlling fly aggression. Connectomic analysis suggests that these neurons have limited connections withfruitlessexpressing neurons that have been shown to be important for aggression, and signal to different descending neurons. Thus, CL062 is part of a monomorphic circuit for aggression that functions parallel to the known dimorphic circuits.
Metal mixtures associate with higher amyotrophic lateral sclerosis risk and mortality independent of genetic risk and correlate to self-reported exposures: a case-control study
Authors: Jang Dae Gyu , Dou John , Koubek Emily J. , Teener Samuel , Zhao Lili , Bakulski Kelly M. , Mukherjee Bhramar , Batterman Stuart A. , Feldman Eva L. , Goutman Stephen A. 
Published: February 2024

ABSTRACTBackgroundThe pathogenesis of amyotrophic lateral sclerosis (ALS) involves both genetic and environmental factors. This study investigates associations between metal measures in plasma and urine, ALS risk and survival, and exposure sources.MethodsParticipants with and without ALS from Michigan provided plasma and urine samples for metal measurement via inductively coupled plasma mass spectrometry. Odds and hazard ratios for each metal were computed using risk and survival models. Environmental risk scores (ERS) were created to evaluate the association between exposure mixtures and ALS risk and survival and exposure source. ALS (ALS-PGS) and metal (metal-PGS) polygenic risk scores were constructed from an independent genome-wide association study and relevant literature-selected SNPs.ResultsPlasma and urine samples from 454 ALS and 294 control participants were analyzed. Elevated levels of individual metals, including copper, selenium, and zinc, significantly associated with ALS risk and survival. ERS representing metal mixtures strongly associated with ALS risk (plasma, OR=2.95, CI=2.38-3.62,p<0.001; urine, OR=3.10, CI=2.43-3.97,p<0.001) and poorer ALS survival (plasma, HR=1.42, CI=1.24-1.63,p<0.001; urine, HR=1.52, CI=1.31-1.76,p<0.001). Addition of the ALS-PGS or metal-PGS did not alter the significance of metals with ALS risk and survival. Occupations with high potential of metal exposure associated with elevated ERS. Additionally, occupational and non-occupational metal exposures associated with measured plasma and urine metals.ConclusionMetals in plasma and urine associated with increased ALS risk and reduced survival, independent of genetic risk, and correlated with occupational and non-occupational metal exposures. These data underscore the significance of metal exposure in ALS risk and progression.
Common and separable neural alterations in adult and adolescent depression – evidence from neuroimaging meta-analyses
Authors: Bore Mercy Chepngetich , Liu Xiqin , Kendrick Keith M , Zhou Bo , Zhang Jie , Klugah-Brown Benjamin , Becker Benjamin 
Published: February 2024

AbstractDepression is a highly prevalent and debilitating disorder that often begins in adolescence. However, it remains unclear whether adults and adolescents with depression exhibit common or separate brain dysfunctions during reward processing. We aimed to identify common and separable neurofunctional alterations during receipt of rewards and brain structure in adolescents and adults with depression. A coordinate-based meta-analysis was employed using Seed-based d mapping with permutation of subject images (SDM-PSI). Compared with healthy controls, both age groups exhibited common activity decreases in the right striatum (putamen, caudate) and subgenual ACC. Adults with depression showed decreased reactivity in the right putamen and subgenual ACC, while adolescents with depression showed decreased activity in the left mid cingulate, right caudate but increased reactivity in the right post central gyrus. This meta-analysis revealed shared (caudate) and separable (putamen and mid cingulate cortex) reward-related alterations in adults and adolescents with depression. The findings suggest age-specific neurofunctional alterations and stress the importance of adolescent-specific interventions that target social functions.
Aging of the Spine: Characterizing genetic and physiological determinants of spinal curvature
Authors: Wang Frances M. , Ruby J. Graham , Sethi Anurag , Veras Matthew , Telis Natalie , Melamud Eugene 
Published: February 2024

AbstractIncreased spinal curvature is one of the most recognizable aging traits in the human population. However, despite high prevalence, the etiology of this condition remains poorly understood. To gain better insight into the physiological, biochemical, and genetic risk factors involved, we developed a novel machine learning method to automatically derive thoracic kyphosis and lumbar lordosis angles from dual-energy X-ray absorptiometry (DXA) scans in the UK Biobank Imaging cohort. In 41,212 participants, we find that on average males and females gain 2.42° kyphotic and 1.48° lordotic angle per decade of life. Increased spinal curvature was strongly associated with decreased muscle mass and bone mineral density. Adiposity had opposing associations, with decreased kyphosis and increased lordosis. To gain further insight into the molecular mechanisms involved, we carried out a genome-wide association study and identified several risk loci associated with both traits. Using Mendelian randomization, we further show that genes fundamental to the maintenance of musculoskeletal function (COL11A1, PTHLH, ETFA, TWIST1) and cellular homeostasis such as RNA transcription and DNA repair (RAD9A, MMS22L, HIF1A, RAB28) are likely involved in increased spinal curvature.
THE SPREAD OF INFECTIOUS DISEASES IN MIGRATION ROUTES BETWEEN CARAVANS AND RESIDENT COMMUNITIES: MODELLING YELLOW FEVER IN CENTRAL AMERICA
Authors: Simon Sabrina Soares , Amaku Marcos , Massad Eduardo 
Published: February 2024

AbstractObjectivesTo investigate the impact of yellow fever (YF) vaccination in the context of an outbreak and its association with migration, by assessing the effects of herd immunity in endemic communities and caravans, and its potential spread to other subsequent at-risk, disease-free communities in the migratory route.MethodsWe use a SEIRV-SEI compartmental deterministic model for humans and vectors and numerical simulations applied to three coupled populations - caravans, endemic and disease-free communities. Two scenarios are evaluated with different vaccination coverage levels at endemic communities and in caravans.ResultsWhen communities endemic to YF are the source of migration, herd immunity is critical, but vaccinating caravans is by far the most significant intervention to protect migrants and disease-free communities upwards from the risk of YF introduction.ConclusionPreventing outbreaks of climate-sensitive infectious diseases in the context of migration must be a joint effort of common interest. Maintaining vaccination coverage at recommended levels combined with the continued effort to vaccinate people on the move is the only intervention that can prevent a health crisis. Therefore, vaccination against climate-sensitive diseases should be considered climate adaptation.