Microcystic macular edema (MME) and inner nuclear layer thickening (INL) were described in multiple sclerosis (MS) and neuromyelitis optica (NMO) patients using optical coherence tomography (OCT). ...The cause of these findings is currently unknown and a relation to inflammatory or degenerative processes in the optic nerve is discussed.
The aim of our study was to investigate whether INL thickening and MME are related to optic neuritis (ON) in various neuro-inflammatory disorders causingON: MS, NMO and chronic inflammatory optic neuropathy.
We retrospectively analyzed data from 216 MS patients, 39 patients with a clinically isolated syndrome, 20 NMO spectrum disorder patients, 9 patients with chronic inflammatory optic neuropathy and 121 healthy subjects. Intra-retinal layer segmentation was performed for the eyes of patients with unilateral ON. Scanning laser ophthalmoscopy (SLO) images were reviewed for characteristic ocular fundus changes.
Intra-retinal layer segmentation showed that eyes with a history of ON displayed MME independent INL thickening compared to contralateral eyes without previous ON. MME was detected in 22 eyes from 15 patients (5.3% of all screened patients), including 7 patients with bilateral edema. Of these, 21 had a prior history of ON (95%). The SLO images of all 22 MME-affected eyes showed crescent-shaped texture changes which were visible in the perifoveal region. A second grader who was blinded to the results of the OCT classified all SLO images for the presence of these characteristic fundus changes. All MME eyes were correctly classified (sensitivity = 100%) with high specificity (95.2%).
This study shows that both MME and INL thickening occur in various neuro-inflammatory disorders associated with ON. We also demonstrate that detection and analysis of MME by OCT is not limited to B-scans, but also possible using SLO images.
Neuromyelitis optica (NMO) and relapsing-remitting multiple sclerosis (RRMS) are difficult to differentiate solely on clinical grounds. Optical coherence tomography (OCT) studies investigating ...retinal changes in both diseases focused primarily on the retinal nerve fiber layer (RNFL) while rare data are available on deeper intra-retinal layers.
To detect different patterns of intra-retinal layer alterations in patients with NMO spectrum disorders (NMOSD) and RRMS with focus on the influence of a previous optic neuritis (ON).
We applied spectral-domain OCT in eyes of NMOSD patients and compared them to matched RRMS patients and healthy controls (HC). Semi-automatic intra-retinal layer segmentation was used to quantify intra-retinal layer thicknesses. In a subgroup low contrast visual acuity (LCVA) was assessed.
NMOSD-, MS- and HC-groups, each comprising 17 subjects, were included in analysis. RNFL thickness was more severely reduced in NMOSD compared to MS following ON. In MS-ON eyes, RNFL thinning showed a clear temporal preponderance, whereas in NMOSD-ON eyes RNFL was more evenly reduced, resulting in a significantly lower ratio of the nasal versus temporal RNFL thickness. In comparison to HC, ganglion cell layer thickness was stronger reduced in NMOSD-ON than in MS-ON, accompanied by a more severe impairment of LCVA. The inner nuclear layer and the outer retinal layers were thicker in NMOSD-ON patients compared to NMOSD without ON and HC eyes while these differences were primarily driven by microcystic macular edema.
Our study supports previous findings that ON in NMOSD leads to more pronounced retinal thinning and visual function impairment than in RRMS. The different retinal damage patterns in NMOSD versus RRMS support the current notion of distinct pathomechanisms of both conditions. However, OCT is still insufficient to help with the clinically relevant differentiation of both conditions in an individual patient.
A GPT-2 Language Model for Biomedical Texts in Portuguese Schneider, Elisa Terumi Rubel; de Souza, Joao Vitor Andrioli; Gumiel, Yohan Bonescki ...
2021 IEEE 34th International Symposium on Computer-Based Medical Systems (CBMS),
2021-June
Conference Proceeding
Electronic health records (EHRs) contain patient-related information formed by structured and unstructured data, a valuable data source for Natural Language Processing (NLP) in the healthcare domain. ...The contextual word embeddings and Transformer-based models have proved their potential, reaching state-of-the-art for various NLP tasks. Although the performance for downstream NLP tasks with free-texts written in English has recently improved, less resource is available considering clinical texts and low-resource languages such as Portuguese. Our objective is to develop a Generative Pre-trained Transformer 2 (GPT-2) language model for Portuguese to support clinical and biomedical NLP tasks. We fine-tuned a generic Portuguese GPT-2 model to corpora of biomedical texts written in Portuguese, using transfer learning. We experimented on a public dataset, manually annotated for detecting patient fall, i.e., a classification task. Our in-domain GPT-2 model outperformed the generic Portuguese GPT-2 model by 3.43 in F1-score (weighted). Our preliminary results show that transfer learning with domain literature can benefit Portuguese biomedical NLP tasks, aligned with other languages' results.
Patients after organ transplantation have impaired immune response after vaccination against the SARS-CoV-2 virus. So far, published studies have reported quite different response rates to SARS-CoV-2 ...vaccination, ranging from 15-79% in liver and kidney transplant recipients. Up to one year after the first vaccine dose, we analyzed the humoral and cellular immune response of 21 liver transplant (LTX) patients after vaccination with mRNA vaccines compared with 28 kidney transplant (KTX) patients. We evaluated IgG against the SARS-CoV-2 spike protein as well as SARS-CoV-2 specific T cells using an ELISpot assay that detected IFN-γ- and/or IL-2-expressing T cells. We found a cellular and/or humoral immune response in 100% of the LTX patients compared with 68% of the KTX patients. Antibody titers against the spike protein of SARS-CoV-2 were significantly higher in the LTX group, and significantly more LTX patients had detectable specific IL-2-producing T cells. The immunosuppression applied in our LTX cohort was lower compared with the KTX cohort (14% triple therapy in LTX patients vs. 79% in KTX patients). One year after the first vaccination, breakthrough infections could be detected in 41% of all organ transplant patients. None of those patients suffered from a severe course of COVID-19 disease, indicating that a partial vaccination response seemed to offer protection to immunosuppressed patients. The better immune response of LTX patients after SARS-CoV-2 vaccination might be due to less intense immunosuppressive therapy compared with KTX patients.
Contextual word embeddings and the Transformers architecture have reached state-of-the-art results in many natural language processing (NLP) tasks and improved the adaptation of models for multiple ...domains. Despite the improvement in the reuse and construction of models, few resources are still developed for the Portuguese language, especially in the health domain. Furthermore, the clinical models available for the language are not representative enough for all medical specialties. This work explores deep contextual embedding models for the Portuguese language to support clinical NLP tasks. We transferred learned information from electronic health records of a Brazilian tertiary hospital specialized in cardiology diseases and pre-trained multiple clinical BERT-based models. We evaluated the performance of these models in named entity recognition experiments, fine-tuning them in two annotated corpora containing clinical narratives. Our pre-trained models outperformed previous multilingual and Portuguese BERT-based models for cardiology and multi-specialty environments, reaching the state-of-the-art for analyzed corpora, with 5.5% F1 score improvement in TempClinBr (all entities) and 1.7% in SemClinBr (Disorder entity) corpora. Hence, we demonstrate that data representativeness and a high volume of training data can improve the results for clinical tasks, aligned with results for other languages.
Motoneurons are not mere output units of neuronal circuits that control motor behavior but participate in pattern generation. Research on the circuit that controls the crawling motor behavior in ...leeches indicated that motoneurons participate as modulators of this rhythmic motor pattern. Crawling results from successive bouts of elongation and contraction of the whole leech body. In the isolated segmental ganglia, dopamine can induce a rhythmic antiphasic activity of the motoneurons that control contraction (DE-3 motoneurons) and elongation (CV motoneurons). The study was performed in isolated ganglia where manipulation of the activity of specific motoneurons was performed in the course of fictive crawling (
). In this study, the membrane potential of CV was manipulated while
was monitored through the rhythmic activity of DE-3. Matching behavioral observations that show that elongation dominates the rhythmic pattern, the electrophysiological activity of CV motoneurons dominates the cycle. Brief excitation of CV motoneurons during
episodes resets the rhythmic activity of DE-3, indicating that CV feeds back to the rhythmic pattern generator. CV hyperpolarization accelerated the rhythm to an extent that depended on the magnitude of the cycle period, suggesting that CV exerted a positive feedback on the unit(s) of the pattern generator that controls the elongation phase. A simple computational model was implemented to test the consequences of such feedback. The simulations indicate that the duty cycle of CV depended on the strength of the positive feedback between CV and the pattern generator circuit.
Rhythmic movements of animals are controlled by neuronal networks that have been conceived as hierarchical structures. At the basis of this hierarchy, we find the motoneurons, few neurons at the top control global aspects of the behavior (e.g., onset, duration); and within these two ends, specific neuronal circuits control the actual rhythmic pattern of movements. We have investigated whether motoneurons are limited to function as output units. Analysis of the network that controls crawling behavior in the leech has clearly indicated that motoneurons, in addition to controlling muscle activity, send signals to the pattern generator. Physiological and modeling studies on the role of specific motoneurons suggest that these feedback signals modulate the phase relationship of the rhythmic activity.
► Fixations organize in clusters tightly following the arithmetic hierarchical tree. ► Syntax in arithmetic is decoded in a glimpse even if constituted by procedurals rules. ► The duration of a ...fixation is predicted by the complexity of the syntactic level. ► Combining syntax and RTs to single operations predicts arithmetic formula RTs.
Mathematics shares with language an essential reliance on the human capacity for recursion, permitting the generation of an infinite range of embedded expressions from a finite set of symbols. We studied the role of syntax in arithmetic thinking, a neglected component of numerical cognition, by examining eye movement sequences during the calculation of arithmetic expressions. Specifically, we investigated whether, similar to language, an expression has to be scanned sequentially while the nested syntactic structure is being computed or, alternatively, whether this structure can be extracted quickly and in parallel. Our data provide evidence for the latter: fixations sequences were stereotypically organized in clusters that reflected a fast identification of syntactic embeddings. A syntactically relevant pattern of eye movement was observed even when syntax was defined by implicit procedural rules (precedence of multiplication over addition) rather than explicit parentheses. While the total number of fixations was determined by syntax, the duration of each fixation varied with the complexity of the arithmetic operation at each step. These findings provide strong evidence for a syntactic organization for arithmetic thinking, paving the way for further comparative analysis of differences and coincidences in the instantiation of recursion in language and mathematics.
A new redox‐active 4,5‐bisguanidino‐substituted o‐benzoquinone ligand L is synthesized, which allows rational access to heterobinuclear complexes through the sequential coordination of two metals. In ...the examples discussed in this work, mononuclear Cu and Pd complexes are prepared in a first coordination step, and these complexes are then used as precursors to homobinuclear CuII‐L0‐CuII and heterobinuclear PdII‐L0‐CuII complexes. In the heterobinuclear complex, the PdII is coordinated by the softer bisguanidine side of L and the CuII by the harder dioxolene side (in line with the HSAB concept). The heterobinuclear complex is in a temperature‐dependent equilibrium with its dimer, with two unsymmetrical Cu‐Cl‐Cu bridges. The redox‐chemistry of the CuII‐L‐CuII and PdII‐L‐CuII complexes is studied. One‐electron oxidation of both complexes was found to be quasi‐reversible in CV experiments, and chemical one‐electron oxidation was achieved with NO+(SbF6−). In the case of the homobinuclear complex L(CuCl2)2+, intramolecular ligand–metal electron‐transfer, triggered by coordination of a CH3CN solvent molecule, leads to a temperature‐dependent equilibrium between the form CuII‐L0‐CuIII at low temperatures (with CH3CN coordinated to the CuIII atom) and CuII‐L⋅+‐CuII at higher temperatures (without CH3CN).
We′re guana have a good time: The new 4,5‐bisguanidino‐substituted o‐benzoquinone ligand L allows rational access to homo‐ and heterobinuclear complexes by the sequential coordination of two metals. Upon one‐electron oxidation of the Cu2 complex, an intramolecular electron‐transfer triggered by coordination is observed.
Background/Objective: Stress is perceived differently across individuals, which might be particularly true for nonclinical and clinical subjects. For this reason, we tested a German adaption of the ...10-item Perceived Stress Scale (PSS-10) for model fit and measurement invariance in a big nonclinical and clinical sample. Method: We (1) conducted multiple confirmatory factor analysis (CFA) in 1,248 nonclinical subjects and 575 outpatients, (2) measurement invariance with multigroup CFA, (3) assessed correlations with relevant constructs and (4) calculated internal consistencies for overall stress and the subscales Helplessness and Self-efficacy. Results: In both samples, CFA revealed a robust two-factorial structure with an excellent model fit. Group comparisons revealed strict measurement invariance. Correlations with associated measures support validity. Internal consistencies were good to very good. Conclusions: We show highly satisfactory psychometric properties of the German PSS-10 for nonclinical and clinical individuals. Measurement invariance analyses demonstrated that varying stress levels of people with a different mental health status are due to true interindividual differences.
Antecedentes/Objetivo: El estrés se percibe de manera diferente entre los individuos, lo que podría ser particularmente cierto para los sujetos no clínicos y clínicos. Por esta razón, probamos una adaptación alemana de la Perceived Stress Scale de 10 ítems (PSS-10) para el ajuste del modelo y la invarianza de la medición en una gran muestra clínica y no clínica. Método: Realizamos (1) un análisis factorial confirmatorio múltiple (CFA) en 1.248 sujetos no clínicos y 575 pacientes ambulatorios, (2) invarianza de medición con CFA multigrupo, (3) correlaciones con constructos relevantes y (4) cálculos de la consistencia interna para la escala general y las subescalas Desvalidez y Autoeficacia. Resultados: En ambas muestras, el CFA reveló una estructura robusta de dos factores con un excelente ajuste del modelo. Las comparaciones grupales indicaron invarianza estricta. Las correlaciones con las medidas asociadas respaldan la validez. Los coeficientes de consistencia interna fueron buenos a muy buenos. Conclusión: Mostramos propiedades psicométricas altamente satisfactorias de la version alemana de la PSS-10 para individuos no clínicos y clínicos. Los análisis de invarianza de medición demostraron que los niveles variables de estrés de las personas con un estado de salud mental diferente se deben a diferencias interindividuales verdaderas.
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