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Scattering of high energy particles from nucleons probes their structure, as was done in the experiments that established the non-zero size of the proton using electron beams1. The use of charged leptons as scattering probes enables measuring the distribution of electric charges, which is encoded in the vector form factors of the nucleon2. Scattering weakly interacting neutrinos gives the opportunity to measure both vector and axial vector form factors of the nucleon, providing an additional, complementary probe of their structure. The nucleon transition axial form factor, FA, can be measured from neutrino scattering from free nucleons, νµn â µ-p and [Formula: see text], as a function of the negative four-momentum transfer squared (Q2). Up to now, FA(Q2) has been extracted from the bound nucleons in neutrino-deuterium scattering3-9, which requires uncertain nuclear corrections10. Here we report the first high-statistics measurement, to our knowledge, of the [Formula: see text] cross-section from the hydrogen atom, using the plastic scintillator target of the MINERvA11 experiment, extracting FA from free proton targets and measuring the nucleon axial charge radius, rA, to be 0.73 ± 0.17 fm. The antineutrino-hydrogen scattering presented here can access the axial form factor without the need for nuclear theory corrections, and enables direct comparisons with the increasingly precise lattice quantum chromodynamics computations12-15. Finally, the tools developed for this analysis and the result presented are substantial advancements in our capabilities to understand the nucleon structure in the weak sector, and also help the current and future neutrino oscillation experiments16-20 to better constrain neutrino interaction models.
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OBJECTIVES: A timely diagnosis is imperative for curing cancer. However, in patients with rheumatic musculoskeletal diseases (RMDs) or paraneoplastic syndromes, misleading symptoms frequently delay cancer diagnosis. As metabolic remodelling characterises both cancer and RMD, we analysed if a metabolic signature can indicate paraneoplasia (PN) or reveal concomitant cancer in patients with RMD. METHODS: Metabolic alterations in the sera of rheumatoid arthritis (RA) patients with (n=56) or without (n=52) a history of invasive cancer were quantified by nuclear magnetic resonance analysis. Metabolites indicative of cancer were determined by multivariable regression analyses. Two independent RA and spondyloarthritis (SpA) cohorts with or without a history of invasive cancer were used for blinded validation. Samples from patients with active cancer or cancer treatment, pulmonary and lymphoid type cancers, paraneoplastic syndromes, non-invasive (NI) precancerous lesions and non-melanoma skin cancer and systemic lupus erythematosus and samples prior to the development of malignancy were used to test the model performance. RESULTS: Based on the concentrations of acetate, creatine, glycine, formate and the lipid ratio L1/L6, a diagnostic model yielded a high sensitivity and specificity for cancer diagnosis with AUC=0.995 in the model cohort, AUC=0.940 in the blinded RA validation cohort and AUC=0.928 in the mixed RA/SpA cohort. It was equally capable of identifying cancer in patients with PN. The model was insensitive to common demographic or clinical confounders or the presence of NI malignancy like non-melanoma skin cancer. CONCLUSIONS: This new set of metabolic markers reliably predicts the presence of cancer in arthritis or PN patients with high sensitivity and specificity and has the potential to facilitate a rapid and correct diagnosis of malignancy.
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Artrite Reumatoide , Metaboloma , Neoplasias , Síndromes Paraneoplásicas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Artrite Reumatoide/sangue , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Neoplasias/sangue , Neoplasias/complicações , Síndromes Paraneoplásicas/sangue , Síndromes Paraneoplásicas/diagnóstico , Idoso , Adulto , Doenças Reumáticas/sangue , Doenças Reumáticas/complicações , Sensibilidade e Especificidade , Biomarcadores Tumorais/sangueRESUMO
OBJECTIVES: In the American regions, Brazil accounts for 97% of visceral leishmaniasis (VL) cases, with a case fatality rate of approximately 10%. This study aimed to investigate the VL mortality distribution in Brazil and identify high-priority and high-risk areas for intervention strategies. STUDY DESIGN: This was an ecological study that analysed the spatial-temporal patterns of VL mortality in Brazilian municipalities. METHODS: Age-standardised VL mortality rates from the Global Burden of Disease study from 2001 to 2018 were used. The distribution of mortality in the municipalities was assessed, and subsequently the Local Index of Spatial Autocorrelation (LISA) analysis was conducted to identify contiguous areas with high mortality rates. Scan analysis identified clusters of high spatial-temporal risks. RESULTS: The highest mortality rates and clusters were in municipalities located in the Northeast region and in the states of Tocantins and Roraima (North region), Mato Grosso do Sul (Central-West region), and Minas Gerais (Southeast region). According to LISA, there was an increase in the number of municipalities classified as high priority from the first 3-year period (n = 434) to the last 3-year period (n = 644). The spatio-temporal analysis identified 21 high-risk clusters for VL mortality. CONCLUSION: Areas with a high risk of VL mortality should prioritise preventing transmission, invest in early diagnosis and treatment, and promote the training of healthcare professionals.
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Cidades , Carga Global da Doença , Leishmaniose Visceral , Análise Espaço-Temporal , Leishmaniose Visceral/mortalidade , Leishmaniose Visceral/epidemiologia , Humanos , Brasil/epidemiologia , Cidades/epidemiologia , Masculino , Adulto , FemininoRESUMO
OBJECTIVES: The objective of this study was to identify Brazil's most critical garbage codes (GCs) reclassified to Chagas disease (ChD) in mortality data and their proportions. We also estimated the potential impact of misclassification on the number of deaths attributed to ChD. STUDY DESIGN: Population-based descriptive study. METHODS: We used the Mortality Information System (SIM; in Portuguese) data before and after routine GC investigation in 2015-2019 to evaluate ChD deaths detected among them. We identified priority GCs, which contributed more than 0.1 % to the percentage of total ChD deaths registered. Spearman's correlation was used to evaluate the association between the reclassification of priority GCs and ChD prevalence. Then, we applied the GC correction factors to estimate the number of deaths attributed to ChD. RESULTS: 22,154 deaths were reported as ChD in the study period. Among them, 1004 deaths originally listed as priority GCs were deaths reclassified to ChD after an investigation in the SIM final database. Unspecific cardiomyopathy (10.2 %), unspecific heart diseases (4.7 %), and heart failure (2.8 %) were GCs with the highest proportions of reclassification to ChD in Brazil. Higher ChD prevalence at the state level was associated with a higher proportion of GC deaths reclassified as ChD. When applying correction factors identified after investigation, we estimated an increase of 26.4 % in registered ChD deaths, mostly in states with higher endemicity. CONCLUSIONS: GCs might conceal deaths due to ChD, particularly in Brazil's states with higher endemicity. The approach suggested in this study may offer an alternative method for estimating ChD-related deaths in endemic countries.
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Doença de Chagas , Cardiopatias , Insuficiência Cardíaca , Humanos , Causas de Morte , Brasil/epidemiologiaRESUMO
In Rheumatoid Arthritis (RA), regulatory T cells (Tregs) have been found to be enriched in the synovial fluid. Despite their accumulation, they are unable to suppress synovial inflammation. Recently, we showed the synovial enrichment of interleukin-9 (IL-9) producing helper T cells and its positive correlation with disease activity. Therefore, we investigated the impact of IL-9 on synovial Tregs in RA. Here, we confirmed high synovial Tregs in RA patients, however these cells were functionally impaired in terms of suppressive cytokine production (IL-10 and TGF-ß). Abrogating IL-9/ IL-9 receptor interaction could restore the suppressive cytokine production of synovial Tregs and reduce the synovial inflammatory T cells producing IFN-γ, TNF-α, IL-17. However, blocking these inflammatory cytokines failed to show any effect on IL-9 producing T cells, highlighting IL-9's hierarchy in the inflammatory network. Thus, we propose that blocking IL-9 might dampen synovial inflammation by restoring Tregs function and inhibiting inflammatory T cells.
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Artrite Reumatoide , Interleucina-9 , Linfócitos T Reguladores , Humanos , Artrite Reumatoide/metabolismo , Citocinas , Inflamação , Interleucina-9/metabolismo , Líquido Sinovial , Membrana Sinovial , Linfócitos T Reguladores/metabolismoRESUMO
This Letter presents the first simultaneous measurement of the quasielasticlike neutrino-nucleus cross sections on C, water, Fe, Pb, and scintillator (hydrocarbon or CH) as a function of longitudinal and transverse muon momentum. The ratio of cross sections per nucleon between Pb and CH is always above unity and has a characteristic shape as a function of transverse muon momentum that evolves slowly as a function of longitudinal muon momentum. The ratio is constant versus longitudinal momentum within uncertainties above a longitudinal momentum of 4.5 GeV/c. The cross section ratios to CH for C, water, and Fe remain roughly constant with increasing longitudinal momentum, and the ratios between water or C to CH do not have any significant deviation from unity. Both the overall cross section level and the shape for Pb and Fe as a function of transverse muon momentum are not reproduced by current neutrino event generators. These measurements provide a direct test of nuclear effects in quasielasticlike interactions, which are major contributors to long-baseline neutrino oscillation data samples.
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Neutrino charged-current quasielastic-like scattering, a reaction category extensively used in neutrino oscillation measurements, probes nuclear effects that govern neutrino-nucleus interactions. This Letter reports the first measurement of the triple-differential cross section for ν_{µ} quasielastic-like reactions using the hydrocarbon medium of the MINERvA detector exposed to a wideband beam spanning 2≤E_{ν}≤20 GeV. The measurement maps the correlations among transverse and longitudinal muon momenta and summed proton kinetic energies, and compares them to predictions from a state-of-art simulation. Discrepancies are observed that likely reflect shortfalls with modeling of pion and nucleon intranuclear scattering and/or spectator nucleon ejection from struck nuclei. The separate determination of leptonic and hadronic variables can inform experimental approaches to neutrino-energy estimation.
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This study aimed to evaluate the filter paper as a means to transport inactivated Gram-negative non-fermentative (GNNF) bacteria and Haemophilus spp. for analysis using MALDI-TOF MS. A total of 133 isolates were evaluated and the analysis of each isolate was performed directly from original bacterial colony and in filter paper after the processing. To evaluate the agreement between the identification performed directly from the colony and after impregnation in filter paper, we assign the scores: >2·3 as excellent (E); 2·0 to 2·3 as very good (VG); 1·7-1·99 as good (G); <1·7 as unidentified (U). The divergences were classified as: Minor Divergence, Intermediate Divergence and Major Divergence. A total of 80 isolates transported in the filter paper disks presented full category concordance; 39 isolates presented Minor Divergence; 4 isolates present Intermediate Divergence; 4 isolates present Major Divergence and 6 isolates present better results after impregnation in filter paper. The proposed methodology of bacteria transportation presented a sensitivity of 96·9% and a specificity of 100%. The filter paper as a means to transport and storage of inactivated GNNF and Haemophilus spp. may be considered a potential tool for faster, more accurate, biosafe and less-expensive identification.
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Bactérias Gram-Negativas , Haemophilus , Bactérias , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodosRESUMO
Macrophages are host cells for parasites of the genus Leishmania where they multiply inside parasitophorous vacuoles. Paradoxically, macrophages are also the cells responsible for killing or controlling parasite growth, if appropriately activated. In this review, we will cover the patterns of macrophage activation and the mechanisms used by the parasite to circumvent being killed. We will highlight the impacts of the vector bite on macrophage activation. Finally, we will discuss the ontogeny of macrophages that are infected by Leishmania spp.
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Citocinas/metabolismo , Leishmaniose/metabolismo , Leishmaniose/parasitologia , Macrófagos/metabolismo , Macrófagos/parasitologia , Animais , Humanos , Leishmania/patogenicidade , Ativação de Macrófagos/fisiologiaRESUMO
We measure neutrino charged-current quasielasticlike scattering on hydrocarbon at high statistics using the wideband Neutrinos at the Main Injector beam with neutrino energy peaked at 6 GeV. The double-differential cross section is reported in terms of muon longitudinal (p_{â¥}) and transverse (p_{â¥}) momentum. Cross section contours versus lepton momentum components are approximately described by a conventional generator-based simulation, however, discrepancies are observed for transverse momenta above 0.5 GeV/c for longitudinal momentum ranges 3-5 and 9-20 GeV/c. The single differential cross section versus momentum transfer squared (dσ/dQ_{QE}^{2}) is measured over a four-decade range of Q^{2} that extends to 10 GeV^{2}. The cross section turnover and falloff in the Q^{2} range 0.3-10 GeV^{2} is not fully reproduced by generator predictions that rely on dipole form factors. Our measurement probes the axial-vector content of the hadronic current and complements the electromagnetic form factor data obtained using electron-nucleon elastic scattering. These results help oscillation experiments because they probe the importance of various correlations and final-state interaction effects within the nucleus, which have different effects on the visible energy in detectors.
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BACKGROUND AND PURPOSE: Neuromodulation is a promising approach to increasing motor recovery in stroke; however, to date, there is a scarcity of evidence documenting the clinical potential of transcranial direct current stimulation (tDCS) administered in the acute phase of stroke. The present study aims to examine the clinical effects of a treatment involving the application of tDCS in the acute stage post-stroke. METHODS: This was a randomized, double-blind, sham-controlled trial. A cohort of 32 stroke patients with severe motor impairment underwent 5 days of treatment with real or sham bi-hemispheric tDCS over the motor cortex. During the treatment, tDCS was applied twice per day (two daily applications each of 15 min), starting 48 to 72 h after stroke onset. RESULTS: We found statistically significant improvements after both real and sham tDCS treatments in primary (hand grip strength, Motricity Index) and secondary (National Institutes of Health Stroke Scale score, Barthel Index) outcomes. Patients receiving real tDCS showed a larger improvement of upper-limb muscle strength at the end of treatment phase; this advantage was no longer present after 6 months. CONCLUSIONS: Transcranial direct current stimulation may be used to accelerate the rate of upper-limb motor recovery during the spontaneous recovery period.
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Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Método Duplo-Cego , Força da Mão , Humanos , Paresia/etiologia , Paresia/terapia , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Resultado do Tratamento , Extremidade SuperiorRESUMO
BACKGROUND AND PURPOSE: Childhood-onset autosomal dominant cerebellar ataxia type 7 (SCA7) is a severe disease which leads to premature loss of ambulation and death. Early diagnosis of SCA7 is of major importance for genetic counselling and still relies on specific genetic testing, driven by clinical expertise. However, the precise phenotype and natural history of paediatric SCA7 has not yet been fully described. Our aims were to describe the natural history of SCA7 in a large multicentric series of children of all ages, and to find correlates to variables defining this natural history. METHODS: We collected and analysed clinical data from 28 children with proven SCA7. All had clinical manifestations of SCA7 and either a definite number of CAG repeats in ATXN7 or a long expansion > 100 CAG. RESULTS: We identified four clinical presentation patterns related to age at onset. Children of all age groups had cerebellar atrophy and retinal dystrophy. Our data, combined with those in the literature, suggest that definite ranges of CAG repeats determine paediatric SCA7 subtypes. The number of CAG repeats inversely correlated to all variables of the natural history. Age at gait ataxia onset correlated accurately to age at loss of walking ability and to age at death. CONCLUSION: SCA7 in children has four presentation patterns that are roughly correlated to the number of CAG repeats. Our depiction of the natural history of SCA7 in children may help in monitoring the effect of future therapeutic trials.
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Ataxias Espinocerebelares , Ataxina-7 , Criança , Testes Genéticos , Humanos , Fenótipo , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/genéticaRESUMO
Black and tan animals have tan-coloured ventral body surfaces separated by sharp boundaries from black-coloured dorsal body surfaces. In the at mouse mutant, a retroviral 6 kb insertion located in the hair cycle-specific promoter of the murine Asip gene encoding agouti signalling protein causes the black and tan phenotype. In rabbits, three ASIP alleles are thought to exist, including an at allele causing a black and tan coat colour that closely resembles the mouse black and tan phenotype. The goal of our study was to identify the functional genetic variant causing the rabbit at allele. We performed a WGS-based comparative analysis of the ASIP gene in one black and tan and three wt agouti-coloured rabbits. The analysis identified 75 at -associated variants including an 11 kb deletion. The deletion is located in the region of the hair cycle-specific ASIP promoter and thus in a region homologous to the site of the retroviral insertion causing the at allele in mice. We observed perfect association of the genotypes at this deletion with the coat colour phenotype in 49 rabbits. The comparative analysis and the previous knowledge about the regulation of ASIP expression suggest that the 11 kb deletion is the most likely causative variant for the black and tan phenotype in rabbits.
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Proteína Agouti Sinalizadora/genética , Éxons , Cor de Cabelo/genética , Regiões Promotoras Genéticas , Coelhos/genética , Deleção de Sequência , Alelos , Animais , FenótipoRESUMO
In the murine model, it was demonstrated that pro-inflammatory cytokines and chemokines are essential to the formation and modulation of Schistosoma-induced granulomatous inflammation. However, the relationship of these immune mediators and disease severity is hard to be established in naturally infected individuals. The current study evaluates the association between plasma concentrations of MIF, sTNF-R1, CCL3, CCL7 and CCL24 and schistosomiasis morbidity in Schistosoma mansoni-infected patients with a low parasite burden. For this propose, 97 S. mansoni-infected individuals were subjected to abdominal ultrasound analysis and clinical examination. Among them, 88 had plasma concentration of immune mediators estimated by ELISA assay. Multivariate linear regression models were used to evaluate the relationship between the plasma concentration of immune mediators and the variables investigated. Although most individuals presented low parasite burden, over 30% of them showed signs of fibrosis defined by ultrasound measurements and 2 patients had a severe form of schistosomiasis. No association between parasite burden and the plasma levels of chemokine/cytokines or disease severity was observed. There was a positive association between plasma concentration of CCL4, sTNF-R1, CCL3 and MIF with gall bladder thickness and/or with portal vein thickness that are liver fibrosis markers. In contrast, no association was found between CCL7 plasma concentrations with any of the schistosomiasis morbidity parameters evaluated. The data showed that CCL24, sTNFR1, MIF and CCL3 can be detected in plasma of S. mansoni-infected individuals and their concentration would be used as prognostic makers of Schistosoma-induced liver fibrosis, even in individuals with low parasite burden.
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Quimiocina CCL24/sangue , Quimiocina CCL3/sangue , Quimiocina CCL7/sangue , Oxirredutases Intramoleculares/sangue , Cirrose Hepática/imunologia , Fatores Inibidores da Migração de Macrófagos/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Schistosoma mansoni/imunologia , Esquistossomose mansoni/imunologia , Adolescente , Adulto , Idoso , Animais , Humanos , Fígado/irrigação sanguínea , Fígado/parasitologia , Fígado/patologia , Cirrose Hepática/parasitologia , Pessoa de Meia-Idade , Veia Porta/patologia , Esquistossomose mansoni/parasitologia , Adulto JovemRESUMO
Final-state kinematic imbalances are measured in mesonless production of ν_{µ}+Aâµ^{-}+p+X in the MINERvA tracker. Initial- and final-state nuclear effects are probed using the direction of the µ^{-}-p transverse momentum imbalance and the initial-state momentum of the struck neutron. Differential cross sections are compared to predictions based on current approaches to medium modeling. These models underpredict the cross section at intermediate intranuclear momentum transfers that generally exceed the Fermi momenta. As neutrino interaction models need to correctly incorporate the effect of the nucleus in order to predict neutrino energy resolution in oscillation experiments, this result points to a region of phase space where additional cross section strength is needed in current models, and demonstrates a new technique that would be suitable for use in fine-grained liquid argon detectors where the effect of the nucleus may be even larger.
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This corrects the article DOI: 10.1103/PhysRevLett.116.071802.
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We report on multinucleon effects in low momentum transfer (<0.8 GeV/c) antineutrino interactions on plastic (CH) scintillator. These data are from the 2010-2011 antineutrino phase of the MINERvA experiment at Fermilab. The hadronic energy spectrum of this inclusive sample is well described when a screening effect at a low energy transfer and a two-nucleon knockout process are added to a relativistic Fermi gas model of quasielastic, Δ resonance, and higher resonance processes. In this analysis, model elements introduced to describe previously published neutrino results have quantitatively similar benefits for this antineutrino sample. We present the results as a double-differential cross section to accelerate the investigation of alternate models for antineutrino scattering off nuclei.
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Neutral-current production of K^{+} by atmospheric neutrinos is a background in searches for the proton decay pâK^{+}ν[over ¯]. Reactions such as νpâνK^{+}Λ are indistinguishable from proton decays when the decay products of the Λ are below detection threshold. Events with K^{+} are identified in MINERvA by reconstructing the timing signature of a K^{+} decay at rest. A sample of 201 neutrino-induced neutral-current K^{+} events is used to measure differential cross sections with respect to the K^{+} kinetic energy, and the non-K^{+} hadronic visible energy. An excess of events at low hadronic visible energy is observed relative to the prediction of the neut event generator. Good agreement is observed with the cross section prediction of the genie generator. A search for photons from π^{0} decay, which would veto a neutral-current K^{+} event in a proton decay search, is performed, and a 2σ deficit of detached photons is observed relative to the genie prediction.
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Charged-current ν_{µ} interactions on carbon, iron, and lead with a final state hadronic system of one or more protons with zero mesons are used to investigate the influence of the nuclear environment on quasielasticlike interactions. The transferred four-momentum squared to the target nucleus, Q^{2}, is reconstructed based on the kinematics of the leading proton, and differential cross sections versus Q^{2} and the cross-section ratios of iron, lead, and carbon to scintillator are measured for the first time in a single experiment. The measurements show a dependence on the atomic number. While the quasielasticlike scattering on carbon is compatible with predictions, the trends exhibited by scattering on iron and lead favor a prediction with intranuclear rescattering of hadrons accounted for by a conventional particle cascade treatment. These measurements help discriminate between different models of both initial state nucleons and final state interactions used in the neutrino oscillation experiments.
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The occurrence of Cynoscion regalis in Portuguese continental waters is reported for the first time, with six specimens collected in 2015 from three areas: Tagus Estuary, Sado Estuary and Praia da Vieira (central-west coast). Analyses of morphometric and meristic characteristics confirmed all six specimens as C. regalis; further validation was obtained by sequencing a 675 bp region of the mitochondrial cytochrome c oxidase I gene. These records constitute a range extension of C. regalis into the southern north-east Atlantic Ocean.