Clinical profiles and related factors in tuberculosis patients with positive sputum smear mycobacterium tuberculosis tests.

The aim of this study was to explore the related factors linked to the development and infectivity of tuberculosis. This was achieved by comparing the clinical characteristics of patients with pulmonary tuberculosis (TB) who tested positive in smear Mycobacterium tuberculosis tests with this who tested negative in smear mycobacterium tests but positive in sputum Gene Xpert tests. We gathered clinical data of 1612 recently hospitalized patients diagnosed with pulmonary tuberculosis who tested positive either in sputum Gene-Xpert test or sputum smear Mycobacterium tuberculosis tests. The data was collected from January 1, 2018 to August 5, 2023, at Sichuan Provincial People's Hospital. We conducted separately analyzes and comparisons of the clinical characteristics between the two groups of patients, aiming to discussed the related factors influencing the development and infectivity of tuberculosis. In comparison to the GeneXpert positive group, the sputum smear positive group exhibited a higher proportion of elderly patients (aged 75-89) and individuals classified as underweight (BMI < 18.5 kg/m2). Furthermore, this group was more prone to experiencing symptoms such as weight loss, coughing and sputum production, hemoptysis, shortness of breath, and difficulty breathing. Moreover, they are also more likely to develop extrapulmonary tuberculosis, such as tuberculous meningitis, tuberculous pleurisy, and tuberculous peritonitis. These clinical features, when present, not only increase the likelihood of a positive result in sputum smear tests but also suggest a high infectivity of pulmonary tuberculosis. Elderly individuals (aged 75 to 89) who are underweight (BMI < 18.5 kg/m2), display symptom of cough, expectoration, hemoptysis and dyspnea-particularly cough and expectoration-and those with extra pulmonary tuberculosis serve as indicators of highly infectious pulmonary tuberculosis patients. These patients may present with more severe condition, carrying a higher bacteria, and being more prone to bacterial elimination. Identification of these patients is crucial, and prompt actions such as timely and rapid isolation measures, cutting off transmission routes, and early empirical treatment of tuberculosis are essential to control the development of the disease.

Endogenous assessment of late gadolinium enhancement grey zone in patients with non-ischaemic cardiomyopathy with T1ρ and native T1 mapping.

AIMS: This study aims to validate and compare the feasibility of T1ρ and native longitudinal relaxation time (T1) mapping in detection of myocardial fibrosis in patients with non-ischaemic cardiomyopathy, focusing on the performance of both methods in identifying late gadolinium enhancement (LGE) grey zone. METHODS AND RESULTS: Twenty-seven hypertrophic cardiomyopathy (HCM) patients, 16 idiopathic dilated cardiomyopathy (DCM) patients, and 18 healthy controls were prospectively enrolled for native T1 and T1ρ mapping imaging and then all the patients underwent enhancement scan for LGE extent and extracellular volume (ECV) values. In LGE positive patients, the LGE areas were divided into LGE core (6 SDs above remote myocardium) and grey zone (2-6 SDs above remote myocardium) according to the signal intensity of LGE. Both HCM and DCM patients showed significantly higher native T1 values and T1ρ values than controls no matter the presence of LGE (all P < 0.01). There were significant differences in native T1 and T1ρ values among four different types of myocardia (LGE core, grey zone, remote area and control, P < 0.0001). However, the T1ρ values of grey zone were significantly higher than control (P < 0.01), while the native T1 values were not (P = 0.089). T1ρ values were significantly associated with both native T1 values (r = 0.54, P < 0.001) and ECV values (r = 0.54, P < 0.001). CONCLUSION: T1ρ mapping is a feasible method to detect myocardial fibrosis in patients with non-ischaemic cardiomyopathy no matter the presence of LGE. Compared with native T1, T1ρ may serve as a better discriminator in the identification of LGE grey zone.

Directed Graphical Models and Causal Discovery for Zero-Inflated Data.

With advances in technology, gene expression measurements from single cells can be used to gain refined insights into regulatory relationships among genes. Directed graphical models are well-suited to explore such (cause-effect) relationships. However, statistical analyses of single cell data are complicated by the fact that the data often show zero-inflated expression patterns. To address this challenge, we propose directed graphical models that are based on Hurdle conditional distributions parametrized in terms of polynomials in parent variables and their 0/1 indicators of being zero or nonzero. While directed graphs for Gaussian models are only identifiable up to an equivalence class in general, we show that, under a natural and weak assumption, the exact directed acyclic graph of our zero-inflated models can be identified. We propose methods for graph recovery, apply our model to real single-cell gene expression data on T helper cells, and show simulated experiments that validate the identifiability and graph estimation methods in practice.

Ceramide on the road to insulin resistance and immunometabolic disorders in transition dairy cows: driver or passenger?

Dairy cows must undergo profound metabolic and endocrine adaptations during their transition period to meet the nutrient requirements of the developing fetus, parturition, and the onset of lactation. Insulin resistance in extrahepatic tissues is a critical component of homeorhetic adaptations in periparturient dairy cows. However, due to increased energy demands at calving that are not followed by a concomitant increase in dry matter intake, body stores are mobilized, and the risk of metabolic disorders dramatically increases. Sphingolipid ceramides involved in multiple vital biological processes, such as proliferation, differentiation, apoptosis, and inflammation. Three typical pathways generate ceramide, and many factors contribute to its production as part of the cell's stress response. Based on lipidomic profiling, there has generally been an association between increased ceramide content and various disease outcomes in rodents. Emerging evidence shows that ceramides might play crucial roles in the adaptive metabolic alterations accompanying the initiation of lactation in dairy cows. A series of studies also revealed a negative association between circulating ceramides and systemic insulin sensitivity in dairy cows experiencing severe negative energy balance. Whether ceramide acts as a driver or passenger in the metabolic stress of periparturient dairy cows is an unknown but exciting topic. In the present review, we discuss the potential roles of ceramides in various metabolic dysfunctions and the impacts of their perturbations. We also discuss how this novel class of bioactive sphingolipids has drawn interest in extrahepatic tissue insulin resistance and immunometabolic disorders in transition dairy cows. We also discuss the possible use of ceramide as a new biomarker for predicting metabolic diseases in cows and highlight the remaining problems.

Generalized score matching for general domains.

Estimation of density functions supported on general domains arises when the data are naturally restricted to a proper subset of the real space. This problem is complicated by typically intractable normalizing constants. Score matching provides a powerful tool for estimating densities with such intractable normalizing constants but as originally proposed is limited to densities on [Formula: see text] and [Formula: see text]. In this paper, we offer a natural generalization of score matching that accommodates densities supported on a very general class of domains. We apply the framework to truncated graphical and pairwise interaction models and provide theoretical guarantees for the resulting estimators. We also generalize a recently proposed method from bounded to unbounded domains and empirically demonstrate the advantages of our method.

Correction: Genetic and metabolomic architecture of variation in diet restriction-mediated lifespan extension in Drosophila.

[This corrects the article DOI: 10.1371/journal.pgen.1008835.].

CorDiffViz: an R package for visualizing multi-omics differential correlation networks.

BACKGROUND: Differential correlation networks are increasingly used to delineate changes in interactions among biomolecules. They characterize differences between omics networks under two different conditions, and can be used to delineate mechanisms of disease initiation and progression. RESULTS: We present a new R package, CorDiffViz, that facilitates the estimation and visualization of differential correlation networks using multiple correlation measures and inference methods. The software is implemented in R, HTML and Javascript, and is available at https://github.com/sqyu/CorDiffViz . Visualization has been tested for the Chrome and Firefox web browsers. A demo is available at https://diffcornet.github.io/CorDiffViz/demo.html . CONCLUSIONS: Our software offers considerable flexibility by allowing the user to interact with the visualization and choose from different estimation methods and visualizations. It also allows the user to easily toggle between correlation networks for samples under one condition and differential correlations between samples under two conditions. Moreover, the software facilitates integrative analysis of cross-correlation networks between two omics data sets.

Genetic and metabolomic architecture of variation in diet restriction-mediated lifespan extension in Drosophila.

In most organisms, dietary restriction (DR) increases lifespan. However, several studies have found that genotypes within the same species vary widely in how they respond to DR. To explore the mechanisms underlying this variation, we exposed 178 inbred Drosophila melanogaster lines to a DR or ad libitum (AL) diet, and measured a panel of 105 metabolites under both diets. Twenty four out of 105 metabolites were associated with the magnitude of the lifespan response. These included proteinogenic amino acids and metabolites involved in α-ketoglutarate (α-KG)/glutamine metabolism. We confirm the role of α-KG/glutamine synthesis pathways in the DR response through genetic manipulations. We used covariance network analysis to investigate diet-dependent interactions between metabolites, identifying the essential amino acids threonine and arginine as "hub" metabolites in the DR response. Finally, we employ a novel metabolic and genetic bipartite network analysis to reveal multiple genes that influence DR lifespan response, some of which have not previously been implicated in DR regulation. One of these is CCHa2R, a gene that encodes a neuropeptide receptor that influences satiety response and insulin signaling. Across the lines, variation in an intronic single nucleotide variant of CCHa2R correlated with variation in levels of five metabolites, all of which in turn were correlated with DR lifespan response. Inhibition of adult CCHa2R expression extended DR lifespan of flies, confirming the role of CCHa2R in lifespan response. These results provide support for the power of combined genomic and metabolomic analysis to identify key pathways underlying variation in this complex quantitative trait.

Generalized Score Matching for Non-Negative Data.

A common challenge in estimating parameters of probability density functions is the intractability of the normalizing constant. While in such cases maximum likelihood estimation may be implemented using numerical integration, the approach becomes computationally intensive. The score matching method of Hyvärinen (2005) avoids direct calculation of the normalizing constant and yields closed-form estimates for exponential families of continuous distributions over R m . Hyvärinen (2007) extended the approach to distributions supported on the non-negative orthant, R + m . In this paper, we give a generalized form of score matching for non-negative data that improves estimation efficiency. As an example, we consider a general class of pairwise interaction models. Addressing an overlooked inexistence problem, we generalize the regularized score matching method of Lin et al. (2016) and improve its theoretical guarantees for non-negative Gaussian graphical models.

[Distribution and risk assessment of HCH and DDT in an abandoned pesticide factory site].

The distribution of HCH (alpha, beta, gamma, delta-HCH) and DDT (p,p'-DDT, o,p'-DDT, p,p'-DDD, p,p'-DDE) in an abandoned pesticide factory site was studied, and its risk assessment was carried out. 232 soil samples were collected from the field 72 points of 0-400 cm depth. Analysis showed that the residual content of HCH and DDT in soil were 2.6-80 130 microg/kg and non-detected-54 350 microg/kg respectively, and showed the characteristics of vertical migration. Both HCH and DDT degraded significantly in this site. The percentages of HCH isomers were alpha-HCH (56.9%) > beta-HCH (23. 3% ) > gamma-HCH (14.0%) > delta-HCH (5.8%), and the percentages of DDT and its metabolites were p,p'-DDT (42.1%) > p,p'-DDD (27.0%) > o,p'-DDT (18.0%) > p,p'-DDE (12.9%). There is no new input source of HCH and DDT at the site soil. The site as a residential land development will not be adverse on residents of non-cancer risk, but non-carcinogenic risk to children is significantly higher than that of adults. At this site, there exists the possibility of cancer risk, and the cancer risk to adults is higher than that to children. Remediation and treatment was necessary for the soil of the site.

[Artesunate combined with vinorelbine plus cisplatin in treatment of advanced non-small cell lung cancer: a randomized controlled trial].

OBJECTIVE: To our knowledge, there has been no clinical report of artesunate in the treatment of lung cancer. This study was designed to compare the efficacy and toxicity of artesunate combined with NP (a chemotherapy regimen of vinorelbine and cisplatin) and NP alone in the treatment of advanced non-small cell lung cancer (NSCLC). METHODS: One hundred and twenty cases of advanced NSCLC were randomly divided into simple chemotherapy group (control group, n=60) and combined artesunare with chemotherapy group (trial group, n=60). Patients in the control group were treated with NP regimen, including vinorelbine (25 mg/m(2), once-a-day intravenous injection, at the 1st and 8th day) and cisplatin (25 mg/m(2), once-a day intravenous drip, at the 2nd to 4th day). Patients in the trial group were treated with the basal therapy NP (in the same method and doses as control group) and artesunate (120 mg, once-a-day intravenous injection, from the 1st day to 8th day, for 8 days). At least two 21-day-cycles of treatment were performed. The short-term survival rate, disease controlled rate (DCR), time to progression (TTP), mean survival time (MST) and 1-year survival rate were analyzed as the primary end points, and the toxicity and safety were estimated. RESULTS: There were no significant differences in the short-term survival rate, MST and 1-year survival rate between the trial group and the control group, which were 45.1% and 34.5%, 44 weeks and 45 weeks, 45.1% and 32.7%, respectively (P>0.05). The DCR of the trial group (88.2%) was significantly higher than that of the control group (72.7%) (P<0.05), and the trial group's TTP (24 weeks) was significantly longer than that of the control group (20 weeks) (P<0.05). No significant difference was found in toxicity between the two groups, such as myelosuppression and digestion reaction (P>0.05). CONCLUSION: Artesunate can be used in the treatment of NSCLC. Artesunate combined with NP can elevate the short-term survival rate and prolong the TTP of patients with advanced NSCLC without extra side effects.

[Experiment of wet FGD process with waste marble].

The wet FGD process with waste marble was studied experimentally, and the mass transfer reaction mechanism was analyzed. Main parameters including liquid/gas ratio, pH value of the absorbent slurry and inlet SO2 concentration, etc. affecting SO2 removal efficiency were studied for the process. The results show that the suitable operating conditions were recommended as follows: pH0 = 5.5-6.5, L/G = 3L/m3, a = 2%; the sulfur dioxide removal efficiency can reach more than 60% when the inlet SO2 concentration was 1000 ml/m3. In addition, the industrial application potential for this process was discussed.