Background
The intestinal microbiota was linked to autoimmune diseases. Graves’ orbitopathy (GO) is an autoimmune disease that is usually associated with Graves’ disease. However, information on the ...microbiome of GO patients is yet lacking.
Objectives
To investigate whether GO patients differ from healthy controls in the fecal microbiota.
Design
A cross-sectional study.
Setting
33 patients with severe and active GO and 32 healthy controls of Han nationality were enrolled between March 2017 and March 2018.
Methods
The Gut microbial communities of the fecal samples of GO patients and healthy controls were analyzed and compared by 16S rRNA gene sequencing.
Results
Community diversity (Simpson and Shannon) was significantly reduced in fecal samples from patients with GO as compared to controls (
p
< 0.05). The similarity observed while assessing the community diversity (PCoA) proposed that the microbiota of patients with GO differ significantly from those of controls (
p
< 0.05). At the phyla levels, the proportion of Bacteroidetes increased significantly in patients with GO (
p
< 0.05), while at the genus and species levels, significant differences were observed in the bacterial profiles between the two groups (
p
< 0.05).
Limitations
Single-centered study design and limited fecal samples.
Conclusions
The present study indicated distinctive features of the gut microbiota in GO patients. The study provided evidence for further exploration in the field of intestinal microbiota with respect to the diagnosis and treatment of GO patients by modifying the microbiota profile.
Reports of ChAdOx1 vaccine-associated thrombocytopenia and vascular adverse events have led to some countries restricting its use. Using a national prospective cohort, we estimated associations ...between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis. An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0-27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41-13.83), with an estimated incidence of 1.13 (0.62-1.63) cases per 100,000 doses. An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29-3.02)). There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12-1.34) 0-27 d after vaccination, with an SCCS RR of 0.97 (0.93-1.02). For hemorrhagic events 0-27 d after vaccination, the aRR was 1.48 (1.12-1.96), with an SCCS RR of 0.95 (0.82-1.11). A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication. Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1. No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events.
Quantum emitters (QEs) coupled to structured baths can localize multiple photons around them and form qubit-photon bound states. In the Markovian or weak coupling regime, the interaction of QEs ...through these single-photon bound states is known to lead to effective many-body QE Hamiltonians with tuneable but yet perturbative interactions. In this work we study the emergence of such models in the non-Markovian or strong coupling regime in different excitation subspaces. The effective models for the non-Markovian regime with up to three excitations are characterized using analytical methods, uncovering the existence of doublons or triplon states. Furthermore, we provide numerical results for systems with multiple excitations and demonstrate the emergence of polariton models with optically tuneable interactions, whose many-body ground state exhibits a superfluid-Mott insulator transition.
We propose a scheme to realize a topological insulator with optical-passive elements and analyze the effects of Kerr nonlinearities in its topological behavior. In the linear regime, our design gives ...rise to an optical spectrum with topological features and where the bandwidths and bandgaps are dramatically broadened. The resulting edge modes cover a very wide frequency range. We relate this behavior to the fact that the effective Hamiltonian describing the system’s amplitudes is long range. We also develop a method to analyze the scheme in the presence of a Kerr medium. We assess robustness and stability of the topological features and predict the presence of chiral squeezed fluctuations at the edges in some parameter regimes.
Background
A previous study indicated that gut microbiota changed notably in Graves’ orbitopathy (GO) patients as compared to controls. However, the characteristics of intestinal bacteria in Graves’ ...disease (GD) and GO are unclear.
Objective
The present study aimed to identify specific intestinal bacteria of GD and GO, respectively.
Methods
The gut microbial communities of the fecal samples of 30 GD patients without GO, 33 GO subjects, and 32 healthy subjects were analyzed and compared by
16S
rRNA gene sequencing.
Results
At the phylum level, the proportion of Deinococcus-Thermus and Chloroflexi was decreased significantly in GO patients as compared to GD. At the genus level, the proportion of Subdoligranulum and Bilophila was increased while that of Blautia, Anaerostipes, Dorea, Butyricicoccus, Romboutsia, Fusicatenibacter, unidentified_ Lachnospiraceae, unidentified_Clostridiales, Collineslla, Intestinibacter, and Phascolarctobacterium was decreased in the GO group as compared to the GD group. Random forest analysis was used for the identification of specific intestinal microbiota, and Deinococcus-Thermus, Cyanobacteria and Chloroflexi were ranked in the top ten according to their contributions to sample classification. Moreover, compared to the control, there were multiple gut bacterial enrichment metabolic pathways in GO and GD patients, including nucleotide metabolism, enzyme family, and energy metabolism. Compared to GO, the only enrichment metabolic pathway found in GD was the viral protein family.
Conclusions
This study highlighted the significant differences in the intestinal microbiota and predictive functions of GD with GO, thereby providing new insights into the role of the gut bacteria that might contribute to the development of GO in GD patients.
A flip-flop circuit hardened against soft errors is presented in this paper. This design is an improved version of Quatro for further enhanced soft-error resilience by integrating the guard-gate ...technique. The proposed design, as well as reference Quatro and regular flip-flops, was implemented and manufactured in a 65-nm CMOS bulk technology. Experimental characterization results of their alpha and heavy ions soft-error rates verified the superior hardening performance of the proposed design over the other two circuits.
Coronavirus disease 2019 (COVID-19) is an emerging infectious disease of pandemic proportions. Healthcare workers in Singapore working in high-risk areas were mandated to wear personal protective ...equipment (PPE) such as N95 face mask and protective eyewear while attending to patients.
We sought to determine the risk factors associated with the development of de novo PPE-associated headaches as well as the perceived impact of these headaches on their personal health and work performance. The impact of COVID-19 on pre-existing headache disorders was also investigated.
This is a cross-sectional study among healthcare workers at our tertiary institution who were working in high-risk hospital areas during COVID-19. All respondents completed a self-administered questionnaire.
A total of 158 healthcare workers participated in the study. Majority 126/158 (77.8%) were aged 21-35 years. Participants included nurses 102/158 (64.6%), doctors 51/158 (32.3%), and paramedical staff 5/158 (3.2%). Pre-existing primary headache diagnosis was present in about a third 46/158 (29.1%) of respondents. Those based at the emergency department had higher average daily duration of combined PPE exposure compared to those working in isolation wards 7.0 (SD 2.2) vs 5.2 (SD 2.4) hours, P < .0001 or medical ICU 7.0 (SD 2.2) vs 2.2 (SD 0.41) hours, P < .0001. Out of 158 respondents, 128 (81.0%) respondents developed de novo PPE-associated headaches. A pre-existing primary headache diagnosis (OR = 4.20, 95% CI 1.48-15.40; P = .030) and combined PPE usage for >4 hours per day (OR 3.91, 95% CI 1.35-11.31; P = .012) were independently associated with de novo PPE-associated headaches. Since COVID-19 outbreak, 42/46 (91.3%) of respondents with pre-existing headache diagnosis either "agreed" or "strongly agreed" that the increased PPE usage had affected the control of their background headaches, which affected their level of work performance.
Most healthcare workers develop de novo PPE-associated headaches or exacerbation of their pre-existing headache disorders.
We introduce a method to investigate the static and dynamic properties of both Abelian and non-Abelian lattice gauge models in 1+1 dimensions. Specifically, we identify a set of transformations that ...disentangle different degrees of freedom, and apply a simple Gaussian variational ansatz to the resulting Hamiltonian. To demonstrate the suitability of the method, we analyze both static and dynamic aspects of string breaking for the U(1) and SU(2) gauge models. We benchmark our results against tensor network simulations and observe excellent agreement, although the number of variational parameters in the Gaussian ansatz is much smaller.
Multidrug-resistant bacterial pathogens are becoming increasingly prevalent, and novel strategies to treat bacterial infections caused by these organisms are desperately needed. Bacterial central ...metabolism is crucial for catabolic processes and provides precursors for anabolic pathways, such as the biosynthesis of essential biomolecules like amino acids or vitamins. However, most essential pathways are not regarded as good targets for antibiotic therapy since their products might be acquired from the environment. This issue raises doubts about the essentiality of such targets during infection. A putative target in bacterial anabolism is the methionine biosynthesis pathway. In contrast to humans, almost all bacteria carry methionine biosynthesis pathways which have often been suggested as putative targets for novel anti-infectives. While the growth of methionine auxotrophic strains can be stimulated by exogenous methionine, the extracellular concentrations required by most bacterial species are unknown. Furthermore, several phenotypic characteristics of methionine auxotrophs are only partly reversed by exogenous methionine. We investigated methionine auxotrophic mutants of
,
, and
(all differing in methionine biosynthesis enzymes) and found that each needed concentrations of exogenous methionine far exceeding that reported for human serum (∼30 µM). Accordingly, these methionine auxotrophs showed a reduced ability to proliferate in human serum. Additionally,
and
methionine auxotrophs were significantly impaired in their ability to form and maintain biofilms. Altogether, our data show intrinsic defects of methionine auxotrophs. This result suggests that the pathway should be considered for further studies validating the therapeutic potential of inhibitors.
New antibiotics that attack novel targets are needed to circumvent widespread resistance to conventional drugs. Bacterial anabolic pathways, such as the enzymes for biosynthesis of the essential amino acid methionine, have been proposed as potential targets. However, the eligibility of enzymes in these pathways as drug targets is unclear because metabolites might be acquired from the environment to overcome inhibition. We investigated the nutritional needs of methionine auxotrophs of the pathogens
,
, and
We found that each auxotrophic strain retained a growth disadvantage at methionine concentrations mimicking those available
and showed that biofilm biomass was strongly influenced by endogenous methionine biosynthesis. Our experiments suggest that inhibition of the methionine biosynthesis pathway has deleterious effects even in the presence of external methionine. Therefore, additional efforts to validate the effects of methionine biosynthesis inhibitors
are warranted.
Batch effects are the systematic non-biological differences between batches (groups) of samples in microarray experiments due to various causes such as differences in sample preparation and ...hybridization protocols. Previous work focused mainly on the development of methods for effective batch effects removal. However, their impact on cross-batch prediction performance, which is one of the most important goals in microarray-based applications, has not been addressed. This paper uses a broad selection of data sets from the Microarray Quality Control Phase II (MAQC-II) effort, generated on three microarray platforms with different causes of batch effects to assess the efficacy of their removal. Two data sets from cross-tissue and cross-platform experiments are also included. Of the 120 cases studied using Support vector machines (SVM) and K nearest neighbors (KNN) as classifiers and Matthews correlation coefficient (MCC) as performance metric, we find that Ratio-G, Ratio-A, EJLR, mean-centering and standardization methods perform better or equivalent to no batch effect removal in 89, 85, 83, 79 and 75% of the cases, respectively, suggesting that the application of these methods is generally advisable and ratio-based methods are preferred.
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