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1.
Immunity ; 56(1): 180-192.e11, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36563676

RESUMO

The reinvigoration of anti-tumor T cells in response to immune checkpoint blockade (ICB) therapy is well established. Whether and how ICB therapy manipulates antibody-mediated immune response in cancer environments, however, remains elusive. Using tandem mass spectrometric analysis of modification of immunoglobulin G (IgG) from hepatoma tissues, we identified a role of ICB therapy in catalyzing IgG sialylation in the Fc region. Effector T cells triggered sialylation of IgG via an interferon (IFN)-γ-ST6Gal-I-dependent pathway. DC-SIGN+ macrophages represented the main target cells of sialylated IgG. Upon interacting with sialylated IgG, DC-SIGN stimulated Raf-1-elicited elevation of ATF3, which inactivated cGAS-STING pathway and eliminated subsequent type-I-IFN-triggered antitumorigenic immunity. Although enhanced IgG sialylation in tumors predicted improved therapeutic outcomes for patients receiving ICB therapy, impeding IgG sialylation augmented antitumorigenic T cell immunity after ICB therapy. Thus, targeting antibody-based negative feedback action of ICB therapy has potential for improving efficacy of cancer immunotherapies.


Assuntos
Carcinoma Hepatocelular , Interferon Tipo I , Neoplasias Hepáticas , Humanos , Imunoglobulina G , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Imunoterapia/métodos
2.
Immunity ; 54(6): 1304-1319.e9, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34048708

RESUMO

Despite mounting evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engagement with immune cells, most express little, if any, of the canonical receptor of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2). Here, using a myeloid cell receptor-focused ectopic expression screen, we identified several C-type lectins (DC-SIGN, L-SIGN, LSECtin, ASGR1, and CLEC10A) and Tweety family member 2 (TTYH2) as glycan-dependent binding partners of the SARS-CoV-2 spike. Except for TTYH2, these molecules primarily interacted with spike via regions outside of the receptor-binding domain. Single-cell RNA sequencing analysis of pulmonary cells from individuals with coronavirus disease 2019 (COVID-19) indicated predominant expression of these molecules on myeloid cells. Although these receptors do not support active replication of SARS-CoV-2, their engagement with the virus induced robust proinflammatory responses in myeloid cells that correlated with COVID-19 severity. We also generated a bispecific anti-spike nanobody that not only blocked ACE2-mediated infection but also the myeloid receptor-mediated proinflammatory responses. Our findings suggest that SARS-CoV-2-myeloid receptor interactions promote immune hyperactivation, which represents potential targets for COVID-19 therapy.


Assuntos
COVID-19/metabolismo , COVID-19/virologia , Interações Hospedeiro-Patógeno , Lectinas Tipo C/metabolismo , Proteínas de Membrana/metabolismo , Células Mieloides/imunologia , Células Mieloides/metabolismo , Proteínas de Neoplasias/metabolismo , SARS-CoV-2/fisiologia , Enzima de Conversão de Angiotensina 2/metabolismo , Sítios de Ligação , COVID-19/genética , Linhagem Celular , Citocinas , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Mediadores da Inflamação/metabolismo , Lectinas Tipo C/química , Proteínas de Membrana/química , Modelos Moleculares , Proteínas de Neoplasias/química , Ligação Proteica , Conformação Proteica , Anticorpos de Domínio Único/imunologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Relação Estrutura-Atividade
3.
Proc Natl Acad Sci U S A ; 120(7): e2215423120, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36745780

RESUMO

Due to the ubiquitous nature of language in the environment of infants, how it affects the anatomical structure of the brain language system over the lifespan is not well understood. In this study, we investigated the effects of early language experience on the adult brain by examining anatomical features of individuals born deaf with typical or restricted language experience in early childhood. Twenty-two deaf adults whose primary language was American Sign Language and were first immersed in it at ages ranging from birth to 14 y participated. The control group was 21 hearing non-signers. We acquired T1-weighted magnetic resonance images and used FreeSurfer [B. Fischl, Neuroimage 62, 774-781(2012)] to reconstruct the brain surface. Using an a priori regions of interest (ROI) approach, we identified 17 language and 19 somatomotor ROIs in each hemisphere from the Human Connectome Project parcellation map [M. F. Glasser et al., Nature 536, 171-178 (2016)]. Restricted language experience in early childhood was associated with negative changes in adjusted grey matter volume and/or cortical thickness in bilateral fronto-temporal regions. No evidence of anatomical differences was observed in any of these regions when deaf signers with infant sign language experience were compared with hearing speakers with infant spoken language experience, showing that the effects of early language experience on the brain language system are supramodal.


Assuntos
Surdez , Pré-Escolar , Humanos , Adulto , Surdez/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Idioma , Audição , Língua de Sinais
4.
J Neurosci ; 44(13)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38383498

RESUMO

Within the intricate matrices of cognitive neuroscience, auditory deprivation acts as a catalyst, propelling a cascade of neuroanatomical adjustments that have, until now, been suboptimally articulated in extant literature. Addressing this gap, our study harnesses high-resolution 3 T MRI modalities to unveil the multifaceted cortical transformations that emerge in tandem with congenital auditory deficits. We conducted a rigorous cortical surface analysis on a cohort of 90 congenitally deaf individuals, systematically compared with 90 normoacoustic controls. Our sample encompassed both male and female participants, ensuring a gender-inclusive perspective in our analysis. Expected alterations within prototypical auditory domains were evident, but our findings transcended these regions, spotlighting modifications dispersed across a gamut of cortical and subcortical structures, thereby epitomizing the cerebral adaptive dynamics to sensory voids. Crucially, the study's innovative methodology integrated two pivotal variables: the duration of auditory deprivation and the extent of sign language immersion. By intersecting these metrics with structural changes, our analysis unveiled nuanced layers of cortical reconfigurations, elucidating a more granulated understanding of neural plasticity. This intersectional approach bestows a unique advantage, allowing for a discerning exploration into how varying durations of sensory experience and alternative communication modalities modulate the brain's morphological terrain. In encapsulating the synergy of neuroimaging finesse and incisive scientific rigor, this research not only broadens the current understanding of adaptive neural mechanisms but also paves the way for tailored therapeutic strategies, finely attuned to individual auditory histories and communicative repertoires.


Assuntos
Córtex Auditivo , Surdez , Humanos , Masculino , Feminino , Imageamento por Ressonância Magnética , Córtex Auditivo/diagnóstico por imagem , Plasticidade Neuronal
5.
Nano Lett ; 24(1): 16-25, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38109350

RESUMO

The anomalous Hall effect (AHE) is an important transport signature revealing topological properties of magnetic materials and their spin textures. Recently, MnBi2Te4 has been demonstrated to be an intrinsic magnetic topological insulator. However, the origin of its intriguing AHE behaviors remains elusive. Here, we demonstrate the Berry curvature-dominated intrinsic AHE in wafer-scale MnBi2Te4 films. By applying back-gate voltages, we observe an ambipolar conduction and n-p transition in ∼7-layer MnBi2Te4, where a quadratic relation between the AHE resistance and longitudinal resistance suggests its intrinsic AHE nature. In particular, for ∼3-layer MnBi2Te4, the AHE sign can be tuned from pristine negative to positive. First-principles calculations unveil that such an AHE reversal originated from the competing Berry curvature between oppositely polarized spin-minority-dominated surface states and spin-majority-dominated inner bands. Our results shed light on the underlying physical mechanism of the intrinsic AHE and provide new perspectives for the unconventional sign-tunable AHE.

6.
J Neurosci ; 43(44): 7376-7392, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37709540

RESUMO

The survival of an organism is dependent on its ability to respond to cues in the environment. Such cues can attain control over behavior as a function of the value ascribed to them. Some individuals have an inherent tendency to attribute reward-paired cues with incentive motivational value, or incentive salience. For these individuals, termed sign-trackers, a discrete cue that precedes reward delivery becomes attractive and desirable in its own right. Prior work suggests that the behavior of sign-trackers is dopamine-dependent, and cue-elicited dopamine in the NAc is believed to encode the incentive value of reward cues. Here we exploited the temporal resolution of optogenetics to determine whether selective inhibition of ventral tegmental area (VTA) dopamine neurons during cue presentation attenuates the propensity to sign-track. Using male tyrosine hydroxylase (TH)-Cre Long Evans rats, it was found that, under baseline conditions, ∼84% of TH-Cre rats tend to sign-track. Laser-induced inhibition of VTA dopamine neurons during cue presentation prevented the development of sign-tracking behavior, without affecting goal-tracking behavior. When laser inhibition was terminated, these same rats developed a sign-tracking response. Video analysis using DeepLabCutTM revealed that, relative to rats that received laser inhibition, rats in the control group spent more time near the location of the reward cue even when it was not present and were more likely to orient toward and approach the cue during its presentation. These findings demonstrate that cue-elicited dopamine release is critical for the attribution of incentive salience to reward cues.SIGNIFICANCE STATEMENT Activity of dopamine neurons in the ventral tegmental area (VTA) during cue presentation is necessary for the development of a sign-tracking, but not a goal-tracking, conditioned response in a Pavlovian task. We capitalized on the temporal precision of optogenetics to pair cue presentation with inhibition of VTA dopamine neurons. A detailed behavioral analysis with DeepLabCutTM revealed that cue-directed behaviors do not emerge without dopamine neuron activity in the VTA. Importantly, however, when optogenetic inhibition is lifted, cue-directed behaviors increase, and a sign-tracking response develops. These findings confirm the necessity of dopamine neuron activity in the VTA during cue presentation to encode the incentive value of reward cues.


Assuntos
Sinais (Psicologia) , Motivação , Ratos , Masculino , Animais , Neurônios Dopaminérgicos , Ratos Sprague-Dawley , Dopamina , Ratos Long-Evans , Recompensa
7.
Neuroimage ; : 120720, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38971484

RESUMO

This meta-analysis summarizes evidence from 44 neuroimaging experiments and characterizes the general linguistic network in early deaf individuals. Meta-analytic comparisons with hearing individuals found that a specific set of regions (in particular the left inferior frontal gyrus and posterior middle temporal gyrus) participates in supramodal language processing. In addition to previously described modality-specific differences, the present study showed that the left calcarine gyrus and the right caudate were additionally recruited in deaf compared with hearing individuals. In addition, this study showed that the bilateral posterior superior temporal gyrus is shaped by cross-modal plasticity, whereas the left frontotemporal areas are shaped by early language experience. Although an overall left-lateralized pattern for language processing was observed in the early deaf individuals, regional lateralization was altered in the inferior temporal gyrus and anterior temporal lobe. These findings indicate that the core language network functions in a modality-independent manner, and provide a foundation for determining the contributions of sensory and linguistic experiences in shaping the neural bases of language processing.

8.
Eur J Neurosci ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39193632

RESUMO

For a subset of individuals known as sign-trackers, discrete Pavlovian cues associated with rewarding stimuli can acquire incentive properties and exert control over behaviour. Because responsiveness to cues is a feature of various neuropsychiatric conditions, rodent models of sign-tracking may prove useful for exploring the neurobiology of individual variation in psychiatric vulnerabilities. Converging evidence points towards the involvement of dopaminergic neurotransmission in the nucleus accumbens core (NAc) in the development of sign-tracking, yet whether this phenotype is associated with specific accumbal postsynaptic properties is unknown. Here, we examined dendritic spine structural organisation, as well as presynaptic and postsynaptic markers of activity, in the NAc core of male and female rats following a Pavlovian-conditioned approach procedure. In contrast to our prediction that cue re-exposure would increase spine density, experiencing the discrete lever-cue without reward delivery resulted in lower spine density than control rats for which the lever was unpaired with reward during training; this effect was tempered in the most robust sign-trackers. Interestingly, this same behavioural test (lever presentation without reward) resulted in increased levels of a marker of presynaptic activity (synaptophysin), and this effect was greatest in female rats. Whilst some behavioural differences were observed in females during initial Pavlovian training, final conditioning scores did not differ from males and were unaffected by the oestrous cycle. This work provides novel insights into how conditioning impacts the neuronal plasticity of the NAc core, whilst highlighting the importance of studying the behaviour and neurobiology of both male and female rats.

9.
Am Nat ; 204(3): E42-E56, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39179232

RESUMO

AbstractMutation rates vary widely along genomes and across inheritance systems. This suggests that complex traits-resulting from the contributions of multiple determinants-might be composite in terms of the underlying mutation rates. Here we investigate through mathematical modeling whether such a heterogeneity may drive changes in a trait's architecture, especially in fluctuating environments, where phenotypic instability can be beneficial. We first identify a convexity principle related to the shape of the trait's fitness function, setting conditions under which composite architectures should be adaptive or, conversely and more commonly, should be selected against. Simulations reveal, however, that applying this principle to realistic evolving populations requires taking into account pervasive epistatic interactions that take place in the system. Indeed, the fate of a mutation affecting the architecture depends on the (epi)genetic background, which itself depends on the current architecture in the population. We tackle this problem by borrowing the adaptive dynamics framework from evolutionary ecology-where it is routinely used to deal with such resident/mutant dependencies-and find that the principle excluding composite architectures generally prevails. Yet the predicted evolutionary trajectories will typically depend on the initial architecture, possibly resulting in historical contingencies. Finally, by relaxing the large population size assumption, we unexpectedly find that not only the strength of selection on a trait's architecture but also its direction depend on population size, revealing a new occurrence of the recently identified phenomenon coined "sign inversion."


Assuntos
Evolução Biológica , Modelos Genéticos , Taxa de Mutação , Fenótipo , Seleção Genética , Epistasia Genética , Mutação
10.
Eur J Immunol ; 53(8): e2250228, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37194443

RESUMO

The advent of highly effective disease modifying therapy has transformed the landscape of multiple sclerosis (MS) care over the last two decades. However, there remains a critical, unmet need for sensitive and specific biomarkers to aid in diagnosis, prognosis, treatment monitoring, and the development of new interventions, particularly for people with progressive disease. This review evaluates the current data for several emerging imaging and liquid biomarkers in people with MS. MRI findings such as the central vein sign and paramagnetic rim lesions may improve MS diagnostic accuracy and evaluation of therapy efficacy in progressive disease. Serum and cerebrospinal fluid levels of several neuroglial proteins, such as neurofilament light chain and glial fibrillary acidic protein, show potential to be sensitive biomarkers of pathologic processes such as neuro-axonal injury or glial-inflammation. Additional promising biomarkers, including optical coherence tomography, cytokines and chemokines, microRNAs, and extracellular vesicles/exosomes, are also reviewed, among others. Beyond their potential integration into MS clinical care and interventional trials, several of these biomarkers may be informative of MS pathogenesis and help elucidate novel targets for treatment strategies.


Assuntos
Esclerose Múltipla , Humanos , Esclerose Múltipla/diagnóstico por imagem , Biomarcadores , Prognóstico , Imageamento por Ressonância Magnética/métodos , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano
11.
Immunol Cell Biol ; 102(7): 593-604, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38757764

RESUMO

Delta inulin, or Advax, is a polysaccharide vaccine adjuvant that significantly enhances vaccine-mediated immune responses against multiple pathogens and was recently licensed for use in the coronavirus disease 2019 (COVID-19) vaccine SpikoGen. Although Advax has proven effective as an immune adjuvant, its specific binding targets have not been characterized. In this report, we identify a cellular receptor for Advax recognition. In vitro uptake of Advax particles by macrophage cell lines was substantially greater than that of latex beads of comparable size, suggesting an active uptake mechanism by phagocytic cells. Using a lectin array, Advax particles were recognized by lectins specific for various carbohydrate structures including mannosyl, N-acetylgalactosamine and galactose moieties. Expression in nonphagocytic cells of dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), a C-type lectin receptor, resulted in enhanced uptake of fluorescent Advax particles compared with mock-transfected cells. Advax uptake was reduced with the addition of ethylenediaminetetraacetic acid and mannan to cells, which are known inhibitors of DC-SIGN function. Finally, a specific blockade of DC-SIGN using a neutralizing antibody abrogated Advax uptake in DC-SIGN-expressing cells. Together, these results identify DC-SIGN as a putative receptor for Advax. Given the known immunomodulatory role of DC-SIGN, the findings described here have implications for the use of Advax adjuvants in humans and inform future mechanistic studies.


Assuntos
Adjuvantes Imunológicos , Moléculas de Adesão Celular , Inulina , Lectinas Tipo C , Receptores de Superfície Celular , Humanos , Adjuvantes Imunológicos/farmacologia , Adjuvantes de Vacinas/metabolismo , Moléculas de Adesão Celular/metabolismo , Linhagem Celular , COVID-19/imunologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Inulina/metabolismo , Inulina/análogos & derivados , Lectinas Tipo C/metabolismo , Macrófagos/metabolismo , Macrófagos/imunologia , Mananas/metabolismo , Receptores de Superfície Celular/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-38759208

RESUMO

OBJECTIVES: To investigate whether hypoechoic wall thickness is influenced by the systole or diastole moment in the cardiac cycle and if this can influence ultrasound (US) assessments of giant cell arteritis (GCA). METHODS: US videos of 100 consecutive patients (50 with GCA, 50 without) performed between January 2021 and June 2023 were reviewed. Intima-media thickness (IMT) of temporal (including common trunk, frontal and parietal branches), axillary and subclavian arteries were measured at two different time points, at systolic peak (SP) and at the end-diastole (ED). Differences between SP IMT and ED IMT, as well as in the halo count (HC) and in the OMERACT GCA Ultrasonography Score (OGUS) between these two times, were analyzed. RESULTS: IMT was significantly higher (4.8-5%) at ED in all arteries, in both GCA and non-GCA groups. HC and OGUS were also higher in ED in both groups. In 4 non-GCA patients (8%), the HC was positive in ED and negative in SP; in all of them the HC in ED was 1. In the GCA group, the timing of the cardiac cycle did not influence the final US diagnosis; however, it did modify the HC in 14 patients (28%). CONCLUSION: IMT can fluctuate during the cardiac cycle, with higher measurements occurring at ED. This variability could potentially impact the accuracy of US diagnoses and assessments of GCA. If further research corroborates these findings, it may be imperative to revise the guidelines for employing US in diagnosing GCA in order to incorporate these nuanced aspects.

13.
J Anat ; 244(1): 63-74, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37694853

RESUMO

The apophyseal growth plate of the greater trochanter, unlike most other growth plates of the human body, exhibits a curved morphology that results in a divergent pattern resembling an open crocodile mouth on plain antero-posterior radiographs. To quantify the angular alignment of the growth plate and to draw conclusions about the function of the muscles surrounding it, we analyzed 57 MRI images of 51 children and adolescents aged 3-17 years and of six adults aged 18-52 years. We measured the angulation of the plate relative to the horizontal plane (AY angle) and the trajectories of the muscles attaching to the greater trochanter of the proximal femur. From anterior to posterior, the AY angle shows a decrease of 33.44°. In the anterior third, the cartilage is angled at a mean of 51.64°, and in the posterior third, the mean angulation is 18.6°. This indicates that the cartilage in the anterior region of the greater trochanteric apophysis is subject to more vertically oriented force vectors compared to the posterior region, as the growth plates align perpendicular to the force vectors acting on them. Combining the measured muscle trajectories with the physiological cross-sectional areas (PCSA) available from the literature revealed that, in addition to the known internal and external lateral traction ligament systems, a third, dorsally located traction ligament system exists that may be responsible for the dorsal deformation of the AY angle.


Assuntos
Lâmina de Crescimento , Articulação do Quadril , Criança , Adulto , Adolescente , Humanos , Lâmina de Crescimento/diagnóstico por imagem , Fenômenos Biomecânicos , Articulação do Quadril/anatomia & histologia , Fêmur/diagnóstico por imagem , Fêmur/fisiologia , Músculos
14.
Neurobiol Learn Mem ; 211: 107915, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38527649

RESUMO

Rat autoshaping procedures generate two readily measurable conditioned responses: During lever presentations that have previously signaled food, rats approach the food well (called goal-tracking) and interact with the lever itself (called sign-tracking). We investigated how reinforced and nonreinforced trials affect the overall and temporal distributions of these two responses across 10-second lever presentations. In two experiments, reinforced trials generated more goal-tracking than sign-tracking, and nonreinforced trials resulted in a larger reduction in goal-tracking than sign-tracking. The effect of reinforced trials was evident as an increase in goal-tracking and reduction in sign-tracking across the duration of the lever presentations, and nonreinforced trials resulted in this pattern transiently reversing and then becoming less evident with further training. These dissociations are consistent with a recent elaboration of the Rescorla-Wagner model, HeiDI (Honey, R.C., Dwyer, D.M., & Iliescu, A.F. (2020a). HeiDI: A model for Pavlovian learning and performance with reciprocal associations. Psychological Review, 127, 829-852.), a model in which responses related to the nature of the unconditioned stimulus (e.g., goal-tracking) have a different origin than those related to the nature of the conditioned stimulus (e.g., sign-tracking).


Assuntos
Condicionamento Clássico , Reforço Psicológico , Animais , Masculino , Ratos , Condicionamento Clássico/fisiologia , Condicionamento Operante/fisiologia , Objetivos , Comportamento Animal/fisiologia
15.
Mult Scler ; 30(1): 25-34, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38088067

RESUMO

BACKGROUND: The central vein sign (CVS) is a proposed magnetic resonance imaging (MRI) biomarker for multiple sclerosis (MS); the optimal method for abbreviated CVS scoring is not yet established. OBJECTIVE: The aim of this study was to evaluate the performance of a simplified approach to CVS assessment in a multicenter study of patients being evaluated for suspected MS. METHODS: Adults referred for possible MS to 10 sites were recruited. A post-Gd 3D T2*-weighted MRI sequence (FLAIR*) was obtained in each subject. Trained raters at each site identified up to six CVS-positive lesions per FLAIR* scan. Diagnostic performance of CVS was evaluated for a diagnosis of MS which had been confirmed using the 2017 McDonald criteria at thresholds including three positive lesions (Select-3*) and six positive lesions (Select-6*). Inter-rater reliability assessments were performed. RESULTS: Overall, 78 participants were analyzed; 37 (47%) were diagnosed with MS, and 41 (53%) were not. The mean age of participants was 45 (range: 19-64) years, and most were female (n = 55, 71%). The area under the receiver operating characteristic curve (AUROC) for the simplified counting method was 0.83 (95% CI: 0.73-0.93). Select-3* and Select-6* had sensitivity of 81% and 65% and specificity of 68% and 98%, respectively. Inter-rater agreement was 78% for Select-3* and 83% for Select-6*. CONCLUSION: A simplified method for CVS assessment in patients referred for suspected MS demonstrated good diagnostic performance and inter-rater agreement.


Assuntos
Esclerose Múltipla , Adulto , Humanos , Feminino , Adulto Jovem , Pessoa de Meia-Idade , Masculino , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Projetos Piloto , Reprodutibilidade dos Testes , Veias , Imageamento por Ressonância Magnética/métodos , Encéfalo/patologia
16.
Am J Med Genet A ; 194(1): 103-106, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37747091

RESUMO

The well-known eye-of-the-tiger sign features bilateral and symmetrical changes in the globus pallidus, with a central area of high signal and peripheral low signal on T2-weighted MRI. Although formally considered pathognomonic of pantothenate kinase-associated neurodegeneration (PKAN), there are other neurodegenerative or genetic diseases showing similar findings. Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a late-onset ataxia, that was recently associated with biallelic AAGGG repeat expansion in the RFC1 gene. Although its predominant MRI finding is cerebellar atrophy, there may be other less common associated findings. Our aim is to present two cases of CANVAS with associated (pseudo-)eye-of-the-tiger sign, highlighting the possibility of yet another differential diagnosis for this imaging sign.


Assuntos
Vestibulopatia Bilateral , Ataxia Cerebelar , Doenças Vestibulares , Humanos , Ataxia Cerebelar/diagnóstico , Ataxia Cerebelar/genética , Vestibulopatia Bilateral/diagnóstico , Vestibulopatia Bilateral/genética , Ataxia , Síndrome , Imageamento por Ressonância Magnética/métodos
17.
Biotechnol Bioeng ; 121(4): 1191-1215, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38221763

RESUMO

Continuous monitoring of vital signs such as respiration and heart rate is essential to detect and predict conditions that may affect the patient's well-being. To detect these vital signs most medical systems use contact sensors. They are not feasible for long term monitoring and are not repeatable. Vital signs using facial video-noncontact monitoring are becoming increasingly important. Researchers in the last few years although considerable progress has been made, challenging datasets absence timing of assessment process and the technology still has some limitations such as time consuming nature and lack of computer portability. To solve those problems, we propose a contactless video based vital signs detection framework for continuous health monitoring using feature optimization and hybrid neural network. In the proposed technique, modified war strategy optimization algorithm is proposed to segment the face portion from the input video frames. Then, we utilize the known data acquisition models to extract vital signs from the segmented face portions are heart rate, blood pressure, respiratory rate and oxygen saturation. An improved neural network structure (Lifting Net) is further used to achieve the adaptive extraction of deep hidden features for specific signs, for realizing the high precision of human health monitoring. The Hughes effect or dimensionality issue affects detection accuracy in sign classification when there are fewer training instances relative to the number of spectral features. The problem can be overcome through feature optimization here Northern goshawk optimization algorithm is used to select optimal best features which reduces the data dimensionality issue. Furthermore, hybrid deep ensemble reinforcement learning classifier is proposed for the human vital sign detection and classification which ensures the early detection of patient abnormality. Finally, we validate our framework using benchmark video datasets such as TokyoTechrPPG, PURE and COHFACE. To proves the effectiveness of proposed technique using simulation results and comparative analysis.


Assuntos
Taxa Respiratória , Sinais Vitais , Humanos , Monitorização Fisiológica/métodos , Sinais Vitais/fisiologia , Redes Neurais de Computação , Frequência Cardíaca
18.
Horm Behav ; 164: 105609, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39083878

RESUMO

Cues in the environment become predictors of biologically relevant stimuli, such as food, through associative learning. These cues can not only act as predictors but can also be attributed with incentive motivational value and gain control over behavior. When a cue is imbued with incentive salience, it attains the ability to elicit maladaptive behaviors characteristic of psychopathology. We can capture the propensity to attribute incentive salience to a reward cue in rats using a Pavlovian conditioned approach paradigm, in which the presentation of a discrete lever-cue is followed by the delivery of a food reward. Upon learning the cue-reward relationship, some rats, termed sign-trackers, develop a conditioned response directed towards the lever-cue; whereas others, termed goal-trackers, approach the food cup upon lever-cue presentation. Here, we assessed the effects of systemic corticosterone (CORT) on the acquisition and expression of sign- and goal-tracking behaviors in male and female rats, while examining the role of the vendor (Charles River or Taconic) from which the rats originated in these effects. Treatment naïve male and female rats from Charles River had a greater tendency to sign-track than those from Taconic. Administration of CORT enhanced the acquisition of sign-tracking behavior in males from Charles River and females from both vendors. Conversely, administration of CORT had no effect on the expression of the conditioned response. These findings demonstrate a role for CORT in cue-reward learning and suggest that inherent tendencies towards sign- or goal-tracking may interact with this physiological mediator of motivated behavior.


Assuntos
Condicionamento Clássico , Corticosterona , Sinais (Psicologia) , Recompensa , Animais , Masculino , Corticosterona/farmacologia , Feminino , Ratos , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Clássico/fisiologia , Motivação/efeitos dos fármacos , Motivação/fisiologia , Caracteres Sexuais , Ratos Sprague-Dawley , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Ratos Long-Evans
19.
Catheter Cardiovasc Interv ; 103(1): 51-60, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37994226

RESUMO

BACKGROUND: Among the two stent strategies, contemporary evidence favors double kissing crush technique (DKC) for complex unprotected distal left main bifurcation (UdLMB) lesions. However one of the major challenges to these lesions is side branch (SB) restenosis. AIMS: Our aim was to identify optical coherence tomographic (OCT) characteristics that may predict SB restenosis (SBR) after UdLMB angioplasty using DKC technique. METHODS: This was a single-center, retrospective study that included 60 patients with complex UdLMB disease, who underwent OCT-guided angioplasty using DKC technique. Angiographic follow-up was performed in all patients at 1 year to identify patients with SBR. Patients with SBR group were compared with patients without SBR (NSBR group) for OCT parameters during index procedure. RESULTS: Twelve (20%) patients developed SBR at 1-year follow-up. The SBR group had longer SB lesion (18.8 ± 3.2 vs. 15.3 ± 3.7 mm, p = 0.004) and neo-metallic carinal length (2.1 vs. 0.1 mm, p < 0.001) when compared to the NSBR group. Longer neo-metallic carinal length was associated with the absence of the dumbbell sign, presence of hanging stent struts across the SB ostium on OCT of final MB pullback. On multivariate regression analysis, SB distal reference diameter (DRD) and SB stent expansion were identified as independent predictors of SBR with SB-DRD of ≤2.8 mm (area under curve-0.73, sensitivity-83.3%, and specificity-62.5%) and SB stent expansion of ≤89% (area under curve-0.88, sensitivity-83.3%, and specificity- 81.2%) as the best cut off values to predict SBR. CONCLUSIONS: SB DRD and SB stent expansion are the OCT predictors of future SBR after UdLMB angioplasty using DKC technique.


Assuntos
Angioplastia Coronária com Balão , Doença da Artéria Coronariana , Stents Farmacológicos , Doenças das Valvas Cardíacas , Humanos , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/métodos , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/cirurgia , Stents , Constrição Patológica , Angiografia Coronária/métodos
20.
Cogn Neuropsychol ; 41(1-2): 1-17, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38377394

RESUMO

ABSTRACTThis study investigates factors influencing lexical access in language production across modalities (signed and oral). Data from deaf and hearing signers were reanalyzed (Baus and Costa, 2015, On the temporal dynamics of sign production: An ERP study in Catalan Sign Language (LSC). Brain Research, 1609(1), 40-53. https://doi.org/10.1016/j.brainres.2015.03.013; Gimeno-Martínez and Baus, 2022, Iconicity in sign language production: Task matters. Neuropsychologia, 167, 108166. https://doi.org/10.1016/j.neuropsychologia.2022.108166) testing the influence of psycholinguistic variables and ERP mean amplitudes on signing and naming latencies. Deaf signers' signing latencies were influenced by sign iconicity in the picture signing task, and by spoken psycholinguistic variables in the word-to-sign translation task. Additionally, ERP amplitudes before response influenced signing but not translation latencies. Hearing signers' latencies, both signing and naming, were influenced by sign iconicity and word frequency, with early ERP amplitudes predicting only naming latencies. These findings highlight general and modality-specific determinants of lexical access in language production.


Assuntos
Eletroencefalografia , Potenciais Evocados , Psicolinguística , Língua de Sinais , Humanos , Masculino , Feminino , Potenciais Evocados/fisiologia , Adulto , Surdez/fisiopatologia , Pessoa de Meia-Idade , Adulto Jovem , Fala/fisiologia
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