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1.
Nature ; 569(7757): E9, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31073227

RESUMO

Change history: In this Letter, the y-axis values in Fig. 3f should go from 4 to -8 (rather than from 4 to -4), the y-axis values in Fig. 3h should appear next to the major tick marks (rather than the minor ticks), and in Fig. 1b, the arrows at the top and bottom of the electron-scale current sheet were going in the wrong direction; these errors have been corrected online.

2.
Nature ; 557(7704): 202-206, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29743689

RESUMO

Magnetic reconnection in current sheets is a magnetic-to-particle energy conversion process that is fundamental to many space and laboratory plasma systems. In the standard model of reconnection, this process occurs in a minuscule electron-scale diffusion region1,2. On larger scales, ions couple to the newly reconnected magnetic-field lines and are ejected away from the diffusion region in the form of bi-directional ion jets at the ion Alfvén speed3-5. Much of the energy conversion occurs in spatially extended ion exhausts downstream of the diffusion region 6 . In turbulent plasmas, which contain a large number of small-scale current sheets, reconnection has long been suggested to have a major role in the dissipation of turbulent energy at kinetic scales7-11. However, evidence for reconnection plasma jetting in small-scale turbulent plasmas has so far been lacking. Here we report observations made in Earth's turbulent magnetosheath region (downstream of the bow shock) of an electron-scale current sheet in which diverging bi-directional super-ion-Alfvénic electron jets, parallel electric fields and enhanced magnetic-to-particle energy conversion were detected. Contrary to the standard model of reconnection, the thin reconnecting current sheet was not embedded in a wider ion-scale current layer and no ion jets were detected. Observations of this and other similar, but unidirectional, electron jet events without signatures of ion reconnection reveal a form of reconnection that can drive turbulent energy transfer and dissipation in electron-scale current sheets without ion coupling.

3.
Syst Biol ; 71(3): 526-546, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-34324671

RESUMO

Introgression is an important biological process affecting at least 10% of the extant species in the animal kingdom. Introgression significantly impacts inference of phylogenetic species relationships where a strictly binary tree model cannot adequately explain reticulate net-like species relationships. Here, we use phylogenomic approaches to understand patterns of introgression along the evolutionary history of a unique, nonmodel insect system: dragonflies and damselflies (Odonata). We demonstrate that introgression is a pervasive evolutionary force across various taxonomic levels within Odonata. In particular, we show that the morphologically "intermediate" species of Anisozygoptera (one of the three primary suborders within Odonata besides Zygoptera and Anisoptera), which retain phenotypic characteristics of the other two suborders, experienced high levels of introgression likely coming from zygopteran genomes. Additionally, we find evidence for multiple cases of deep inter-superfamilial ancestral introgression. [Gene flow; Odonata; phylogenomics; reticulate evolution.].


Assuntos
Odonatos , Animais , Genoma , Insetos/anatomia & histologia , Odonatos/anatomia & histologia , Odonatos/genética , Filogenia
4.
Phys Rev Lett ; 126(11): 113202, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33798343

RESUMO

We report the observation of quantum interference between electron wave packets launched from the inner-shell 4d orbital of the Xe atom. Using pairs of femtosecond radiation wave packets from a synchrotron light source, we obtain time-domain interferograms for the inner-shell excitations. This approach enables the experimental verification and control of the quantum interference between the electron wave packets. Furthermore, the femtosecond Auger decay of the inner-shell excited state is tracked. To the best of our knowledge, this is the first observation of wave packet interference in an atomic inner-shell process, and also the first time-resolved experiment on few-femtosecond Auger decay using a synchrotron light source.

5.
Br J Dermatol ; 182(2): 410-417, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31049930

RESUMO

BACKGROUND: The European League Against Rheumatism/American College of Rheumatology classification criteria for inflammatory myopathies are able to classify patients with skin-predominant dermatomyositis (DM). However, approximately 25% of patients with skin-predominant DM do not meet two of the three hallmark skin signs and fail to meet the criteria. OBJECTIVES: To develop a set of skin-focused classification criteria that will distinguish cutaneous DM from mimickers and allow a more inclusive definition of skin-predominant disease. METHODS: An extensive literature review was done to generate items for the Delphi process. Items were grouped into categories of distribution, morphology, symptoms, antibodies, histology and contextual factors. Using REDCap™, participants rated these items in terms of appropriateness and distinguishing ability from mimickers. The relevance score ranged from 1 to 100, and the median score determined a rank-ordered list. A prespecified median score cut-off was decided by the steering committee and the participants. There was a pre-Delphi and two rounds of actual Delphi. RESULTS: There were 50 participating dermatologists and rheumatologists from North America, South America, Europe and Asia. After a cut-off score of 70 during the first round, 37 of the initial 54 items were retained and carried over to the next round. The cut-off was raised to 80 during round two and a list of 25 items was generated. CONCLUSIONS: This project is a key step in the development of prospectively validated classification criteria that will create a more inclusive population of patients with DM for clinical research. What's already known about this topic? Proper classification of patients with skin-predominant dermatomyositis (DM) is indispensable in the appropriate conduct of clinical/translational research in the field. The only validated European League Against Rheumatism/American College of Rheumatology criteria for idiopathic inflammatory myopathies are able to classify skin-predominant DM. However, a quarter of amyopathic patients still fail the criteria and does not meet the disease classification. What does this study add? A list of 25 potential criteria divided into categories of distribution, morphology, symptomatology, pathology and contextual factors has been generated after several rounds of consensus exercise among experts in the field of DM. This Delphi project is a prerequisite to the development of a validated classification criteria set for skin-predominant DM.


Assuntos
Dermatomiosite , Reumatologia , Ásia , Técnica Delphi , Dermatomiosite/diagnóstico , Europa (Continente) , Humanos , América do Norte
6.
J Phys Chem A ; 124(32): 6478-6485, 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32786233

RESUMO

We present an experimental and theoretical investigation of the photon interaction with formic acid in the vacuum-ultraviolet energy range. The absolute absorption cross sections and ionization efficiencies were measured in the 11.2-21.4 and 13.5-21.4 eV ranges, respectively, using a double-ion chamber technique. Photoionization and neutral-decay cross sections were derived from these results. From the present ionization cross sections and previously reported ionic dissociative branching ratios, the partial cross sections for dissociating processes were obtained. Theoretically, the photoionization cross sections and the asymmetry parameters of the photoelectron angular distributions for ionization out of the six outermost valence orbitals (10a', 2a″, 9a', 1a″, 8a', and 7a') were obtained in the energy range from near-threshold to 35 eV. For that, the Padé approximant technique along with the single-center partial-wave expansion method was applied to solve the Lippmann-Schwinger equation in the static-exchange-polarization level of approximation. This is the first theoretical investigation concerning the determination of the asymmetry parameters and photoionization cross sections of formic acid in the vacuum-ultraviolet energy range. Comparison is made between our results and the previous ones.

7.
Phys Rev Lett ; 123(23): 233401, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31868498

RESUMO

We report on the use of pairs of 10-cycle extreme ultraviolet wave packets with attosecond-controlled spacing emitted by individual relativistic electrons within an electron bunch passing through a tandem undulator. Based on the temporal coherent control technique with circular polarization, we succeeded in controlling the excited state alignment in the photoexcitation of helium atoms, which we verified through the observation of oscillation in fluorescence yield depending on the attosecond-controlled delay time. Our work demonstrates the potential of undulator radiation for the generation of longitudinally coherent wave packets suitable for attosecond coherent control, an application which has hitherto been hidden in the incoherent nature of the radiation pulse emitted by a bunch of electrons.

8.
Br J Dermatol ; 180(2): 373-381, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29953582

RESUMO

BACKGROUND: Application of deep-learning technology to skin cancer classification can potentially improve the sensitivity and specificity of skin cancer screening, but the number of training images required for such a system is thought to be extremely large. OBJECTIVES: To determine whether deep-learning technology could be used to develop an efficient skin cancer classification system with a relatively small dataset of clinical images. METHODS: A deep convolutional neural network (DCNN) was trained using a dataset of 4867 clinical images obtained from 1842 patients diagnosed with skin tumours at the University of Tsukuba Hospital from 2003 to 2016. The images consisted of 14 diagnoses, including both malignant and benign conditions. Its performance was tested against 13 board-certified dermatologists and nine dermatology trainees. RESULTS: The overall classification accuracy of the trained DCNN was 76·5%. The DCNN achieved 96·3% sensitivity (correctly classified malignant as malignant) and 89·5% specificity (correctly classified benign as benign). Although the accuracy of malignant or benign classification by the board-certified dermatologists was statistically higher than that of the dermatology trainees (85·3% ± 3·7% and 74·4% ± 6·8%, P < 0·01), the DCNN achieved even greater accuracy, as high as 92·4% ± 2·1% (P < 0·001). CONCLUSIONS: We have developed an efficient skin tumour classifier using a DCNN trained on a relatively small dataset. The DCNN classified images of skin tumours more accurately than board-certified dermatologists. Collectively, the current system may have capabilities for screening purposes in general medical practice, particularly because it requires only a single clinical image for classification.


Assuntos
Aprendizado Profundo , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias Cutâneas/diagnóstico , Pele/diagnóstico por imagem , Conjuntos de Dados como Assunto , Dermatologistas/estatística & dados numéricos , Dermoscopia , Humanos , Interpretação de Imagem Assistida por Computador/instrumentação , Interpretação de Imagem Assistida por Computador/estatística & dados numéricos , Aplicativos Móveis , Sensibilidade e Especificidade , Smartphone
9.
Br J Dermatol ; 180(4): 881-887, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30120913

RESUMO

BACKGROUND: Myositis-specific autoantibodies (MSAs) are associated with unique clinical subsets in polymyositis/dermatomyositis (PM/DM). Autoantibodies against transcriptional intermediary factor (TIF)-1γ and TIF-1α are known to be MSAs. Previously, we reported that TIF-1ß is also targeted in patients with DM with or without concomitant anti-TIF-1α/γ antibodies. OBJECTIVES: To evaluate the clinical features of seven cases with anti-TIF-1ß antibodies alone. METHODS: Serum autoantibody profiles were determined, and protein and RNA immunoprecipitation studies were conducted. Western blotting was performed to confirm autoantibody reactivity against TIF-1ß. RESULTS: Anti-TIF-1ß antibody was identified by immunoprecipitation assay in 24 cases. Among them, seven patients were positive for anti-TIF-1ß antibody alone. Six of the seven patients were classified as having DM. Among the six cases of DM, two patients had no muscle weakness and normal creatine kinase (CK) levels, and were classified as having clinically amyopathic DM. Four patients had muscle weakness, but three of them had normal serum CK levels that responded well to systemic steroids. Characteristic features of DM included skin rashes, such as Gottron sign, periungual erythema, punctate haemorrhage on the perionychium and facial erythema including heliotrope, which were observed in 86%, 57%, 86% and 71% of our cases, respectively. One of the seven patients had appendiceal cancer. None of the patients had interstitial lung disease. CONCLUSIONS: Seven patients were confirmed to have anti-TIF-1ß antibody without any other MSAs, including TIF-1α/γ antibodies, and six of them were diagnosed with DM. We suggest that anti-TIF-1ß antibody is an MSA, and that it is associated with clinically amyopathic DM or DM with mild myopathy.


Assuntos
Autoanticorpos/imunologia , Dermatomiosite/imunologia , Proteína 28 com Motivo Tripartido/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Autoanticorpos/isolamento & purificação , Dermatomiosite/sangue , Dermatomiosite/diagnóstico , Feminino , Humanos , Imunoprecipitação , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
Bioinformatics ; 33(1): 125-127, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-27614349

RESUMO

Detecting homologous sequences in organisms is an essential step in protein structure and function prediction, gene annotation and phylogenetic tree construction. Heuristic methods are often employed for quality control of putative homology clusters. These heuristics, however, usually only apply to pairwise sequence comparison and do not examine clusters as a whole. We present the Orthology Group Cleaner (the OGCleaner), a tool designed for filtering putative orthology groups as homology or non-homology clusters by considering all sequences in a cluster. The OGCleaner relies on high-quality orthologous groups identified in OrthoDB to train machine learning algorithms that are able to distinguish between true-positive and false-positive homology groups. This package aims to improve the quality of phylogenetic tree construction especially in instances of lower-quality transcriptome assemblies. AVAILABILITY AND IMPLEMENTATION: https://github.com/byucsl/ogcleaner CONTACT: sfujimoto@gmail.comSupplementary information: Supplementary data are available at Bioinformatics online.


Assuntos
Algoritmos , Proteínas/química , Proteômica/métodos , Análise de Sequência de Proteína/métodos , Homologia de Sequência de Aminoácidos , Anotação de Sequência Molecular , Filogenia , Conformação Proteica , Proteínas/genética , Proteínas/metabolismo
11.
Microb Ecol ; 75(1): 22-37, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28674774

RESUMO

Characterization of interactions within a host-associated microbiome can help elucidate the mechanisms of microbial community formation on hosts and can be used to identify potential probiotics that protect hosts from pathogens. Microbes employ various modes of antagonism when interacting with other members of the community. The formation of biofilm by some strains can be a defense against antimicrobial compounds produced by other taxa. We characterized the magnitude of antagonistic interactions and biofilm formation of 25 phylogenetically diverse taxa that are representative of isolates obtained from egg surfaces of the threatened fish species lake sturgeon (Acipenser fulvescens) at two ecologically relevant temperature regimes. Eight isolates exhibited aggression to at least one other isolate. Pseudomonas sp. C22 was found to be the most aggressive strain, while Flavobacterium spp. were found to be one of the least aggressive and the most susceptible genera. Temperature affected the prevalence and intensity of antagonism. The aggressive strains identified also inhibited growth of known fish pathogens. Biofilm formations were observed for nine isolates and were dependent on temperature and growth medium. The most aggressive of the isolates disrupted biofilm formation of two well-characterized isolates but enhanced biofilm formation of a fish pathogen. Our results revealed the complex nature of interactions among members of an egg associated microbial community yet underscored the potential of specific microbial populations as host probiotics.


Assuntos
Antibiose , Bactérias/isolamento & purificação , Biofilmes , Peixes/microbiologia , Óvulo/microbiologia , Animais , Bactérias/classificação , Bactérias/genética , Fenômenos Fisiológicos Bacterianos , Lagos/microbiologia , Filogenia
12.
Acta Anaesthesiol Scand ; 62(3): 304-311, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29178460

RESUMO

BACKGROUND: Rocuronium can prevent the obturator jerk during transurethral resection of bladder tumors. We investigated the adequate rocuronium dose required for complete block of the thigh adductor muscles, and its correlation with individual responses of the adductor pollicis muscle to rocuronium. METHODS: Eleven patients scheduled for transurethral resection of bladder tumors under general anesthesia were investigated. After general anesthesia induction, neuromuscular monitoring of the adductor pollicis muscle and ultrasonography-guided stimulation of the obturator nerve was commenced. Rocuronium, 0.15 mg/kg, was repeatedly administered intravenously. The adequate rocuronium dose required for complete block of the thigh muscles, defined as the cumulative dose of rocuronium administered until that time, and its correlation with the first twitch response of the adductor pollicis muscle on train-of-four stimulation after initial rocuronium administration was analyzed. RESULTS: The rocuronium dose found adequate for complete block of the thigh muscles was 0.30 mg/kg in seven patients and 0.45 mg/kg in the remaining four patients, which did not correlate with the first twitch response. At the time of complete block of the thigh muscles, the neuromuscular blockade level of the adductor pollicis muscle varied greatly, although the level was never more profound than a post-tetanic count of 1. CONCLUSION: Although the response of the adductor pollicis muscle to rocuronium cannot be used to determine the adequate rocuronium dose required for complete block of the thigh muscles, intense blockade, with maintenance of post-tetanic count at ≤ 1 in the adductor pollicis muscle is essential to prevent the obturator jerk.


Assuntos
Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Rocurônio/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Coxa da Perna , Neoplasias da Bexiga Urinária/cirurgia
13.
Bioinformatics ; 32(1): 17-24, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26382194

RESUMO

MOTIVATION: The contig orientation problem, which we formally define as the MAX-DIR problem, has at times been addressed cursorily and at times using various heuristics. In setting forth a linear-time reduction from the MAX-CUT problem to the MAX-DIR problem, we prove the latter is NP-complete. We compare the relative performance of a novel greedy approach with several other heuristic solutions. RESULTS: Our results suggest that our greedy heuristic algorithm not only works well but also outperforms the other algorithms due to the nature of scaffold graphs. Our results also demonstrate a novel method for identifying inverted repeats and inversion variants, both of which contradict the basic single-orientation assumption. Such inversions have previously been noted as being difficult to detect and are directly involved in the genetic mechanisms of several diseases. AVAILABILITY AND IMPLEMENTATION: http://bioresearch.byu.edu/scaffoldscaffolder. CONTACT: paulmbodily@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Algoritmos , Mapeamento de Sequências Contíguas/métodos
14.
Mol Ecol ; 26(5): 1306-1322, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27758014

RESUMO

Gene duplication plays a central role in adaptation to novel environments by providing new genetic material for functional divergence and evolution of biological complexity. Several evolutionary models have been proposed for gene duplication to explain how new gene copies are preserved by natural selection, but these models have rarely been tested using empirical data. Opsin proteins, when combined with a chromophore, form a photopigment that is responsible for the absorption of light, the first step in the phototransduction cascade. Adaptive gene duplications have occurred many times within the animal opsins' gene family, leading to novel wavelength sensitivities. Consequently, opsins are an attractive choice for the study of gene duplication evolutionary models. Odonata (dragonflies and damselflies) have the largest opsin repertoire of any insect currently known. Additionally, there is tremendous variation in opsin copy number between species, particularly in the long-wavelength-sensitive (LWS) class. Using comprehensive phylotranscriptomic and statistical approaches, we tested various evolutionary models of gene duplication. Our results suggest that both the blue-sensitive (BS) and LWS opsin classes were subjected to strong positive selection that greatly weakens after multiple duplication events, a pattern that is consistent with the permanent heterozygote model. Due to the immense interspecific variation and duplicability potential of opsin genes among odonates, they represent a unique model system to test hypotheses regarding opsin gene duplication and diversification at the molecular level.


Assuntos
Evolução Molecular , Duplicação Gênica , Odonatos/genética , Opsinas/genética , Animais , Genes de Insetos , Heterozigoto , Filogenia
15.
Phys Rev Lett ; 118(9): 094801, 2017 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-28306317

RESUMO

We theoretically demonstrate for the first time that a single free electron in circular or spiral motion emits twisted photons carrying well-defined orbital angular momentum along the axis of the electron circulation, in adding to spin angular momentum. We show that, when the electron velocity is relativistic, the radiation field contains harmonic components and the photons of lth harmonic carry lℏ total angular momentum for each. This work indicates that twisted photons are naturally emitted by free electrons and are more ubiquitous in laboratories and in nature than ever thought.

16.
Mol Psychiatry ; 21(10): 1460-6, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26782053

RESUMO

Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.


Assuntos
Encéfalo/fisiopatologia , Esquizofrenia/fisiopatologia , Adulto , Tonsila do Cerebelo , Gânglios da Base , Mapeamento Encefálico , Estudos de Coortes , Estudos Transversais , Feminino , Lateralidade Funcional/fisiologia , Hipocampo , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Putamen , Tálamo
17.
Br J Dermatol ; 177(5): 1442-1446, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28346662

RESUMO

Autoantibodies to melanoma differentiation-associated protein 5 (MDA5) are associated with a subset of patients with dermatomyositis (DM) who have rapidly progressive interstitial lung disease (RP-ILD) with poor prognosis. Intensive immunosuppressive therapy is initiated before irreversible lung damage can occur; however, there are few lines of evidence for the treatment of RP-ILD. Here, we report three cases of anti-MDA5 antibody-associated DM with RP-ILD in which the patients were treated with combined-modality therapy, including high-dose prednisolone, tacrolimus, intravenous cyclophosphamide and intravenous immunoglobulin (IVIG). In all three cases, serum ferritin levels, which are known to represent the disease activity of RP-ILD, were decreased after IVIG administration. IVIG might contribute to the control of the disease activity of anti-MDA5 antibody-positive DM. Moreover, palmar violaceous macules/papules around the interphalangeal joints, which was observed in all three cases in the incipient stage, might be a useful sign in suggesting a diagnosis of anti-MDA5 antibody-associated DM.


Assuntos
Dermatomiosite/prevenção & controle , Dermatoses da Mão/prevenção & controle , Imunoglobulinas Intravenosas/uso terapêutico , Helicase IFIH1 Induzida por Interferon/imunologia , Doenças Pulmonares Intersticiais/prevenção & controle , Idoso , Anti-Inflamatórios/administração & dosagem , Autoanticorpos/sangue , Terapia Combinada , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Tacrolimo/administração & dosagem , Resultado do Tratamento
18.
Br J Dermatol ; 176(2): 395-402, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27452897

RESUMO

BACKGROUND: Antimelanoma differentiation-associated protein (anti-MDA)5 antibodies are associated with rapidly progressive interstitial lung disease (RP-ILD) in patients with clinically amyopathic dermatomyositis (CADM) or dermatomyositis (DM). OBJECTIVES: We aimed to evaluate the relevance of monitoring anti-MDA5 antibody levels for the management of RP-ILD in patients with CADM or DM. METHODS: Twelve patients with CADM (n = 10) or DM (n = 2) accompanied by RP-ILD were included. Baseline characteristics and outcomes were recorded. Serial measurements of anti-MDA5 antibody levels were measured. All patients were treated with corticosteroids, tacrolimus and intravenous cyclophosphamide. RESULTS: All patients achieved RP-ILD remission after combined immunosuppressive therapy for a mean of 6·8 months, with significant decreases noted in the mean anti-MDA5 antibody levels at remission. Six (50%) patients became anti-MDA5 antibody negative after therapy. After a mean follow-up of 31 months, RP-ILD relapse was observed in four (33%) patients in both the anti-MDA5 antibody sustained positive group and the negative conversion group. However, relapsed patients in the sustained positive group relapsed earlier than those in the negative conversion group. Thus, a decrease in anti-MDA5 antibody levels during remission was associated with longer remission. Relapses were associated with a reincrease of anti-MDA5 antibody levels in four of four (100%) patients. In contrast, none of the patients without reincrease in anti-MDA5 antibody exhibited symptoms of relapse during follow-up. Therefore, reincrease in anti-MDA5 antibody levels was associated with relapse. CONCLUSIONS: The anti-MDA5 antibody level is a novel parameter for monitoring and a good predictor of RP-ILD relapse in patients with CADM or DM.


Assuntos
Dermatomiosite/imunologia , Doenças Pulmonares Intersticiais/imunologia , Corticosteroides/uso terapêutico , Autoanticorpos/metabolismo , Ciclofosfamida/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Dermatomiosite/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/uso terapêutico , Helicase IFIH1 Induzida por Interferon/imunologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Recidiva , Resultado do Tratamento
20.
BMC Bioinformatics ; 17: 101, 2016 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-26911862

RESUMO

BACKGROUND: Accurate detection of homologous relationships of biological sequences (DNA or amino acid) amongst organisms is an important and often difficult task that is essential to various evolutionary studies, ranging from building phylogenies to predicting functional gene annotations. There are many existing heuristic tools, most commonly based on bidirectional BLAST searches that are used to identify homologous genes and combine them into two fundamentally distinct classes: orthologs and paralogs. Due to only using heuristic filtering based on significance score cutoffs and having no cluster post-processing tools available, these methods can often produce multiple clusters constituting unrelated (non-homologous) sequences. Therefore sequencing data extracted from incomplete genome/transcriptome assemblies originated from low coverage sequencing or produced by de novo processes without a reference genome are susceptible to high false positive rates of homology detection. RESULTS: In this paper we develop biologically informative features that can be extracted from multiple sequence alignments of putative homologous genes (orthologs and paralogs) and further utilized in context of guided experimentation to verify false positive outcomes. We demonstrate that our machine learning method trained on both known homology clusters obtained from OrthoDB and randomly generated sequence alignments (non-homologs), successfully determines apparent false positives inferred by heuristic algorithms especially among proteomes recovered from low-coverage RNA-seq data. Almost ~42 % and ~25 % of predicted putative homologies by InParanoid and HaMStR respectively were classified as false positives on experimental data set. CONCLUSIONS: Our process increases the quality of output from other clustering algorithms by providing a novel post-processing method that is both fast and efficient at removing low quality clusters of putative homologous genes recovered by heuristic-based approaches.


Assuntos
Aprendizado de Máquina , Homologia de Sequência , Reações Falso-Positivas , Alinhamento de Sequência
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