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Severe fever with thrombocytopenia syndrome (SFTS) is a novel tick-borne infectious disease caused by a new type of SFTS virus (SFTSV). Here, a longitudinal sampling study is conducted to explore the differences in transcript levels after SFTSV infection, and to characterize the transcriptomic and epigenetic profiles of hospitalized patients. The results reveal significant changes in the mRNA expression of certain genes from onset to recovery. Moreover, m 6 A-seq reveals that certain genes related with immune regulation may be regulated by m 6 A. Besides the routine tests such as platelet counts, serum ALT and AST levels testing, distinct changes in myocardial enzymes, coagulation function, and inflammation are well correlated with the clinical data and sequencing data, suggesting that clinical practitioners should monitor the above indicators to track disease progression and guide personalized treatment. In this study, the transcript changes and RNA modification may lend a fresh perspective to our understanding of the SFTSV and play a significant role in the discovery of drugs for effective treatment of this disease. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever caused by tick-borne SFTS virus. Here, Wang et al. characterize transcriptomic and epigenetic changes in infected patients and correlate them with clinical parameters to improve the understanding of disease progression.

Background Primary adrenal insufficiency (PAI) is a common endocrine complication in AIDS patients, but the diagnosis is often delayed due to the atypical clinic symptoms, which may result in a life-threatening adrenal crisis. Result In this report we present the clinical data of three patients with AIDS and PAI, summarizing the etiology, clinical characteristics, treatment and prognosis. All enrolled three patients were male, aged between 32 and 54 years. Their CD4 + T lymphocyte count (CD4 count) were 58 cells/µL, 378 cells/µL and 35 cells/µL respectively. Two patients had cytomegalovirus (CMV) infection and one had tuberculosis (TB), which were considered to be the main etiologies for PAI. The reported cases exhibited nonspecific clinical symptoms, including fatigue, weight loss, vomiting, diarrhea, anorexia, and fever. All three patients had skin and mucous membrane hyperpigmentation, and two experienced adrenal crisis characterized by intractable hypotension and hyponatremia. Laboratory results revealed low cortisol and higher adrenocorticotropic hormone (ACTH) in serum. All patients responded well to glucocorticoid replacement therapy. By follow-up, their CD4 counts increased steadily. Conclusions In patients with AIDS, especially those with opportunistic infection such as CMV infection or TB, PAI should be considered when symptoms of glucocorticoid deficiency are present. Conversely, in AIDS patients diagnosed with PAI, potential underlying infections such as CMV or TB should be actively investigated.

Background Information on the comparison of blood microbiota between human immunodeficiency virus (HIV)-infected and HIV-uninfected patients with suspected sepsis by metagenomic next-generation sequencing (mNGS) is limited. Methods Retrospectively analysis was conducted in HIV-infected and HIV-uninfected patients with suspected sepsis at Changsha First Hospital (China) from March 2019 to August 2022. Patients who underwent blood mNGS testing were enrolled. The blood microbiota detected by mNGS were analyzed. Results A total of 233 patients with suspected sepsis who performed blood mNGS were recruited in this study, including 79 HIV-infected and 154 HIV-uninfected patients. Compared with HIV-uninfected patients, the proportions of mycobacterium ( p  = 0.001), fungus ( p  < 0.001) and viruses ( p  < 0.001) were significantly higher, while the proportion of bacteria ( p  = 0.001) was significantly lower in HIV-infected patients. The higher positive rates of non-tuberculous mycobacteriosis (NTM, p  = 0.022), Pneumocystis jirovecii ( P. jirovecii ) ( p  = 0.014), Talaromyces marneffei ( T. marneffei ) ( p  < 0.001) and cytomegalovirus (CMV) ( p  < 0.001) were observed in HIV-infected patients, compared with HIV-uninfected patients. In addition, compared with HIV-uninfected patients, the constituent ratio of T. marneffei ( p  < 0.001) in the fungus spectrum were significantly higher, while the constituent ratios of Candida ( p  < 0.001) and Aspergillus ( p  = 0.001) were significantly lower in HIV-infected patients. Conclusions Significant differences in the blood microbiota profiles exist between HIV-infected and HIV-uninfected patients with suspected sepsis.

The influence maximization problem that has drawn a great deal of attention from researchers aims to identify a subset of influential spreaders that can maximize the expected influence spread in social networks. Existing works on the problem primarily concentrate on developing non-adaptive policies, where all seeds will be ignited at the very beginning of the diffusion after the identification. However, in non-adaptive policies, budget redundancy could occur as a result of some seeds being naturally infected by other active seeds during the diffusion process. In this paper, the adaptive seeding policies are investigated for the intractable adaptive influence maximization problem. Based on deep learning model, a novel approach named graph convolutional networks with self-attention mechanism (ATGCN) is proposed to address the adaptive influence maximization as a regression task. A controlling parameter is introduced for the adaptive seeding model to make a tradeoff between the spreading delay and influence coverage. The proposed approach leverages the self-attention mechanism to dynamically assign importance weight to node representations efficiently to capture the node influence feature information relevant to the adaptive influence maximization problem. Finally, intensive experimental findings on six real-world social networks demonstrate the superiorities of the adaptive seeding policy over the state-of-the-art baseline methods to the conventional influence maximization problem. Meanwhile, the proposed adaptive seeding policy ATGCN improves the influence spread rate by up to 7% in comparison to the existing state-of-the-art greedy-based adaptive seeding policy.

We conducted a retrospective, observational study among acquired immune deficiency syndrome (AIDS) patients with cryptococcal meningitis or talaromycosis to assess AmB formulations-related adverse events (AEs). Total 205 eligible patients were enrolled. Of them, 139 received AmB therapy, 51 received liposomal AmB (L-AmB) therapy, and 15 received AmB cholesteryl sulfate complex (ABCD) therapy. The incidences of total AEs between the AmB, L-AmB and ABCD group had no significant differences. The ABCD group had significantly higher incidences of hepatotoxicity and hematological toxicity than the AmB and L-AmB groups. The incidence of grade 3–4 hematological toxicity in the ABCD group was significantly higher than that in the AmB and L-AmB groups. Multinomial logistic regression models showed that compared with AmB, ABCD had a higher risk for the occurrence of grade 3–4 hematological toxicity (aOR = 43.924, 95%CI 6.296-306.418; p  < 0.001). We demonstrated that ABCD was more prone to hepatotoxicity and hematological toxicity than AmB and L-AmB among AIDS patients, which is worth noting.

To evaluate clinical value of metagenomic next-generation sequencing (mNGS) in people living with HIV/AIDS (PLWHA) who had CNS disorders. Cerebrospinal fluid (CSF) samples from 48 PLWHA presenting with CNS disorders were sequenced using mNGS and compared with clinical conventional diagnostic methods. In total, 36/48 ss(75%) patients were diagnosed with pathogen(s) infection by mNGS, and the positive detection proportion by mNGS was higher than that by clinical conventional diagnostic methods (75% vs 52.1%, X 2  = 5.441, P  = 0.020). Thirteen out of 48 patients (27.1%) were detected with 3–7 pathogens by mNGS. Moreover, 77 pathogen strains were detected, of which 94.8% (73/77) by mNGS and 37.0% (30/77) by clinical conventional methods ( X 2  = 54.206, P  < 0.001). The sensitivity and specificity of pathogens detection by mNGS were 63.9% (23/36) and 66.7% (8/12), respectively, which were superior to that by clinical conventional methods (23/36 vs 9/25, X 2  = 4.601, P  = 0.032; 8/12 vs 5/23, X 2  = 5.029, P  = 0.009). The application of mNGS was superior for its ability to detect a variety of unknown pathogens and multiple pathogens infection, and relatively higher sensitivity and specificity in diagnosis of CNS disorders in PLWHA.

Metagenomic next-generation sequencing (mNGS) was suggested to potentially replace traditional microbiological methods because of its comprehensiveness. However, the diagnostic utility of mNGS for tissue hasn’t been fully explored, especially for patient with HIV infection. HIV-positive and negative patients with suspected infectious diseases who performed tissue mNGS and conventional microbiological tests (CMTs) were retrospectively enrolled between October, 2020 and May 2024. The microbial spectrum of tissue mNGS and CMTs was analyzed, and the diagnostic accuracy and consistency of mNGS and CMTs for tissue were compared. The related factors of positive rate of mNGS was analyzed. Of 70 patients with suspected infectious diseases, 44 cases were confirmed with the infectious diseases. Among 44 patients with infectious diseases, aerobic bacteria (36.4%) was the most common detected pathogen, followed by mycobacterium tuberculosis (MTB, 18.2%), non-tuberculous mycobacteria (NTM, 13.6%) and fungus (11.4%). The sensitivity of tissue mNGS (72.7%, 95%CI 56.9%-84.5%) was significantly higher than that that in tissue CMTs (29.5%, 95%CI 17.2%-45.4%) (p<0.001), but the specificity was not statistically significant(P = 0.656). mNGS demonstrated higher detection rates than CMTs in the case with single microbial infections (70.0% vs. 30.0%; p<0.01). For the case with multiple microbial infections, the detection rates of mNGS and CMTs was 100.0% and 25.5% (p=1.000), respectively. Both positive mNGS and CMTs were observed in 22.7% patients with infectious diseases, and sole positive mNGS and sole positive CMTs were observed in 50.0% and 6.8% patients, respectively. There were no statistically differences in age, gender, HIV infection, PCT levels, neutrophil counts, CD4 + lymphocyte count and antibiotic exposure between mNGS positive and mNGS negative groups (P > 0.05). Tissue mNGS could provide a higher sensitivity, more robust and broader method for pathogen identification by comparison with CMTs. However, CMTs shouldn’t be ignored since the low consistency between CMTs and mNGS.

Currently the responses of peripheral cytokine-secreting cells in the natural course of human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection haven't been fully elucidated. The function of peripheral proinflammatory, regulatory and cytotoxic cytokine-secreting cells were investigated by direct intracellular cytokine staining (ICS) and flow cytometry, additionally, the absolute numbers of different cytokine-secreting cells were measured among patients with HIV/TB co-infection (HT group), and compared them with the healthy controls (HC group), patients with TB (TB group) and patients with HIV infection (HIV group). After one week's anti-TB treatment, the changes of the percentages of cytokine-secreting cells were further evaluated in TB and HT groups. Totally 26 individuals in the HC group, 51 in the TB group, 26 in the HIV group and 29 in the HT group were enrolled. The HT. HT group exhibited significantly lower absolute numbers of IFN-γ CD4 , IFN-γ CD8 , TNF-α CD4 , IL17A CD4 T cells and TNF-α CD14 monocytes than the TB and HIV groups. Compared with the TB group, the percentages of CD8 T cells secreting IFN-γ and perforin (p=0.010; p=0.043) were significantly lower among the HT group. Compared with the HIV group, the percentages of CD4 , CD8 T cells and CD14 monocytes secreting TNF-α (p=0.013; p=0.001; p<0.001) were significantly decreased, and the percentage of CD8 T cells secreting IL-17A (p=0.015) was significantly increased among the HT group. Both the percentages of CD4 T cells secreting TGF-β (p<0.001; p=0.001), and CD4 and CD8 T cells secreting granzyme A (all p<0.001), were significantly higher among the HT group than among the TB group and HIV group. After one week's anti-TB treatment, an increased percentage of CD4 T cells secreting TNF-α (p=0.003) was found in the TB group, and an increased percentage of CD8 T cells secreting TNF-α (p=0.029) was found in the HT group. Significantly different functional profiles of peripheral proinflammatory, regulatory, and cytotoxic cytokine-secreting cells were observed in the natural course of HIV/TB co-infection compared to TB and HIV infection alone, even though the absolute numbers of those cells were significantly lower in HIV/TB co-infection. TNF-α-secreting CD8 T cells may be a more sensitive marker for early evaluation of anti-TB treatment efficacy in patients with HIV/TB co-infection.

The most challenge of influence maximization (IM) is to locate a finite set of influencers while maximizing the influence dissemination in a social network. Due to the increasingly widespread and complex application scenarios of IM problem, how to solve the problem effectively remains as a prominent research hotspot. However, most of the existing IM algorithms tend to prioritize either lightweight computational time or solution accuracy, which are hard to be acquired simultaneously. Therefore, considering the trade-off between efficiency and effectiveness, a novel discrete hybrid optimizer by integrating butterfly optimization algorithm (BOA) with differential evolution (DE), named DBOA-DE, is proposed in this paper. An adaptive probability is designed to guide the two operations in the hybrid optimizer, where BOA shows excellent exploratory characteristics by simulating the behavior of butterfly swarms, while DE performs local exploitation through mutation and crossover procedures. Furthermore, in expectation of enhancing the solution accuracy, an improved local search policy is conceived to avoid DBOA-DE from falling into local optimum. Extensive experiments on six real-world social networks show that DBOA-DE outperforms baseline algorithms on influence propagation while maintaining acceptable efficiency, which validate the promising effectiveness and efficiency of the proposed algorithm for IM problems.

Co-infection of visceral leishmaniasis (VL) and human immunodeficiency virus type 1 (HIV-1) is known to have higher rates of initial treatment failure, relapse and mortality than in those without HIV-1 infection. Co-infection of VL and HIV-1 usually results in death by the end of treatment in previously reported cases in China. Here we report on a patient with VL and HIV-1 co-infection who received a high dose and an extended course of sodium stibogluconate treatment in addition to antiretroviral therapy (ART). This treatment regimen resulted in good control of VL and HIV-1 infection, while the conventional protocol of sodium stibogluconate treatment was not able to prevent multiple VL relapses. To the best of our knowledge, this is the first surviving case of VL and HIV-1 co-infection with this particular treatment regimen in China.