Neural manifold analysis of brain circuit dynamics in health and disease

Recent developments in experimental neuroscience make it possible to simultaneously record the activity of thousands of neurons. However, the development of analysis approaches for such large-scale neural recordings have been slower than those applicable to single-cell experiments. One approach that has gained recent popularity is neural manifold learning. This approach takes advantage of the fact that often, even though neural datasets may be very high dimensional, the dynamics of neural activity tends to traverse a much lower-dimensional space. The topological structures formed by these low-dimensional neural subspaces are referred to as “neural manifolds”, and may potentially provide insight linking neural circuit dynamics with cognitive function and behavioral performance. In this paper we review a number of linear and non-linear approaches to neural manifold learning, including principal component analysis (PCA), multi-dimensional scaling (MDS), Isomap, locally linear embedding (LLE), Laplacian eigenmaps (LEM), t-SNE, and uniform manifold approximation and projection (UMAP). We outline these methods under a common mathematical nomenclature, and compare their advantages and disadvantages with respect to their use for neural data analysis. We apply them to a number of datasets from published literature, comparing the manifolds that result from their application to hippocampal place cells, motor cortical neurons during a reaching task, and prefrontal cortical neurons during a multi-behavior task. We find that in many circumstances linear algorithms produce similar results to non-linear methods, although in particular cases where the behavioral complexity is greater, non-linear methods tend to find lower-dimensional manifolds, at the possible expense of interpretability. We demonstrate that these methods are applicable to the study of neurological disorders through simulation of a mouse model of Alzheimer’s Disease, and speculate that neural manifold analysis may help us to understand the circuit-level consequences of molecular and cellular neuropathology

Hanseni?ase: uma revisa?o de literatura / Leprosy: a literature review

INTRODUC?A?O: A Hanseni?ase, doenc?a infecciosa cro?nica granulomatosa, e? causada pelo bacilo a?lcool-acido resistente, Mycobaterium leprae, e afeta a humanidade desde os tempos antigos; pore?m, seu tratamento so? foi descoberto em 1940. Esta doenc?a e? conhecida, principalmente, por ser um fardo moral e social, sendo, portanto, muito estigmatizada. OBJETIVO: Este trabalho foi realizado com a finalidade de reunir dados da literatura para tentar elucidar a doenc?a com o intuito de auxiliar na melhor compreensa?o como um todo da hanseni?ase. DISCUSSA?O: A hanseni?ase e? uma doenc?a que inflige sumariamente os nervos e a derme, podendo provocar danos severos e irreversi?veis.

Escleroderma diabeticorum: rara mas frequentemente na?o reconhecida complicac?a?o da diabetes mellitus / Scleroderma diabeticorum: rare but often not recognized complication of diabetes mellitus

INTRODUC?A?O: O scleroderma adultorum (SA) e? uma doenc?a rara do tecido conjuntivo, caracterizada por endurecimento da pele, geralmente em pescoc?o, ombros e tronco. De etiologia desconhecida e ini?cio insidioso, pode diminuir a mobilidade dos tecidos afetados. Por ser raro e causa de morbidade significativa, e? muito importante seu reconhecimento. METODOLOGIA: O relato do caso consistiu nas informac?o?es obtidas por meio de revisa?o do prontua?rio e entrevista com paciente, bem como na revisa?o de literatura com busca no PubMed/MEDLINE e Scielo acerca do tema. Foram utilizados os termos: “Dermatology” e “Scleroderma, Systemic”. RELATO DO CASO: paciente homem, 60 anos, com quadro insidioso ha? 4 anos de placas eritemato-infiltradas em pescoc?o e dorso. Diabe?tico ha? 20 anos, mal- controlado. Trigliceri?deos de 600, Hemoglobina glicada de 9; micologico direto e cultura para fungos negativos; histopatolo?gico com edema de?rmico e infiltrado de mononucleares perivasculares. Diagno?stico de esclerederma diabeticorum. Paciente evoluiu com melhora do controle glice?mico e amolecimento das placas. DISCUSSA?O: O reconhecimento dessa condic?a?o cuta?nea pode permitir o diagno?stico e tratamento precoce de DM, melhorando o progno?stico e qualidade de vida dos pacientes.1.                  Sattar MA, Diab S, Sugathan TN et al. Scleroedema diabeticorum: a minor but often unrecognized complication of diabetes mellitus. Diabet Med 1988;5:465-8. 2.                  Knobler, R., Moinzadeh, P., Hunzelmann, N., Kreuter, A., Cozzio, A., Mouthon, Krieg, T, et al. European dermatology forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 2: Scleromyxedema, scleredema and nephrogenic systemic fibrosis. Journal of the European Academy of Dermatology and Venereology. 2017;31(10),1581–1594. 3. Tran K, Boyd KP, Robinson MR, Whitlow M. Scleredema diabeticorum. Dermatol Online J. 2013;19:207–18

Necro?lise Epide?rmica To?xica desencadeada por fenitoi?na: Um Relato de caso / Toxic Epidermal Necrolysis Triggered by Phenytoin: A Case Report

INTRODUC?A?O:A necro?lise epide?rmica to?xicae? desencadeada na maior parte das vezes por medicac?o?es, sendo caracterizada por necrose extensiva da epiderme acometendo mais de 30% da superfi?cie corpo?rea, levando o paciente a apresentar aspecto de grande queimado. As medicac?o?es mais comumente associadas sa?o o alopurinol, lamotrigina, sulfassalazina, anti-inflamato?rios na?o esteroidais e fa?rmacos oncolo?gicos. OBJETIVO: Neste estudo, discutimos os principais aspectos da necro?lise epide?rmica to?xica atrave?s de uma revisa?o de literatura ilustrada por um caso cli?nico. METODOLOGIA: Foi realizada uma revisa?o bibliogra?fica tomando-se por refere?ncia informac?o?es obtidas nas bases de dados online PubMed e SciELO. Artigos em ingle?s, portugue?s, france?s e espanhol foram inclui?dos e ilustrados com um caso cli?nico. RELATO DO CASO: O paciente analisado foi admitido no servic?o com leso?es descamativo bolhosas em 40% da superfi?cie corporal, hematu?ria macrosco?pica e taquicardia 48 horas apo?s uso de fenitoi?na. O paciente foi tratado na unidade de queimados, com suspensa?o da medicac?a?o e curativos seriados e teve um curso favora?vel da doenc?a sem sequelas. DISCUSSA?O: Apresentamos dados para orientar o tratamento de pacientes com necro?lise epide?rmica to?xica para cirurgio?es pla?sticos, pediatras, intensivistas, dermatologistas e me?dicos de emerge?ncia. Um alto ni?vel de suspeita e? necessa?rio para um diagno?stico e estratificac?a?o de risco adequados, e medidas e tratamento precoces de apoio devem ser realizados por uma equipe multidisciplinar treinada para minimizar os danos e a mortalidade. 

Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum