3,164 results on '"latent infection"'
Search Results
2. HBHA induces IL-10 from CD4+ T cells in patients with active tuberculosis but IFN-γ and IL-17 from individuals with Mycobacterium tuberculosis infection.
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Izumida, Mai, Jobe, Haddijatou, Coker, Edward G., Barry, Amadou, Rashid, Momodou, Manneh, Ismaila L., Daffeh, Georgetta K., Ariyoshi, Koya, and Sutherland, Jayne S.
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LATENT infection ,MYCOBACTERIUM tuberculosis ,MYCOBACTERIAL diseases ,TRANSVERSE electromagnetic cells ,IMMUNOLOGIC memory - Abstract
Background: To effectively control tuberculosis (TB), it is crucial to distinguish between active TB disease and latent TB infection (LTBI) to provide appropriate treatment. However, no such tests are currently available. Immune responses associated with active TB and LTBI are dynamic and exhibit distinct patterns. Comparing these differences is crucial for developing new diagnostic methods and understanding the etiology of TB. This study aimed to investigate the relationship between pro- and anti-inflammatory CD4+ cytokine production following stimulation with two types of latency-associated Mycobacterium tuberculosis (M.tb) antigens to allow differentiation between active TB and LTBI. Methods: Cryopreserved PBMCs from patients with active TB disease or LTBI were stimulated overnight with replication-related antigen [ESAT-6/CFP-10 (E/C)] or two latency-associated antigens [heparin-binding hemagglutinin (HBHA) and alpha-crystallin-like protein (Acr)]. Responses were analyzed using multiparameter flow cytometry: active TB disease (n=15), LTBI (n=15) and ELISA: active TB disease (n=26) or LTBI (n=27). Results: CD4+ central memory T cells (Tcm) specific to E/C and CD4+ effector memory T cells specific to Acr and HBHA were higher in LTBI than inTB patients. IFN-γ+Tcm and IL-17+ Tem cells was higher in the LTBI group (p= 0.012 and p=0.029 respectively), but IL-10+ Tcm was higher in the active TB group (p= 0.029) following HBHA stimulation. Additionally, following stimulation with HBHA, IL-10 production from CD4+ T cells was significantly elevated in patients with active TB compared to those with LTBI (p= 0.0038), while CD4+ T cell production of IL-17 and IFN-γ was significantly elevated in LTBI compared to active TB (p= 0.0076, p< 0.0001, respectively). HBHA also induced more CCR6 + IL-17+CD4Tcells and IL-17+FoxP3+CD25+CD4Tcells in LTBI than in TB patients (P=0.026 and P=0.04, respectively). HBHA also induced higher levels of IFN-γ+IL-10+CD4+ T cells in patients with active TB (Pp=0.03) and higher levels of IFN-γ+IL-17+ CD4+ T cells in those with LTBI (p=0.04). HBHA-specific cytokine production measured using ELISA showed higher levels of IFN-γ in participants with LTBI (P=0.004) and higher levels of IL-10 in those with active TB (P=0.04). Conclusion: Stimulation with HBHA and measurement of CD4+ T cell production of IFN-γ, IL-10, and IL-17 could potentially differentiate active TB from LTBI. The characteristics of cytokine-expressing cells induced by HBHA also differed between participants with active TB and LTBI. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Essential phage component induces resistance of bacterial community.
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Qianyu Hu, Liang Huang, Yaoyu Yang, Ye Xiang, and Jintao Liu
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LATENT infection , *DRUG resistance in bacteria , *KLEBSIELLA infections , *BACTERIAL communities , *KLEBSIELLA pneumoniae , *BIOFILMS - Abstract
Despite extensive knowledge on phage resistance at bacterium level, the resistance of bacterial communities is still not well-understood. Given its ubiquity, it is essential to understand resistance at the community level. We performed quantitative investigations on the dynamics of phage infection in Klebsiella pneumoniae biofilms. We found that the biofilms quickly developed resistance and resumed growth. Instead of mutations, the resistance was caused by unassembled phage tail fibers released by the phage-lysed bacteria. The tail fibers degraded the bacterial capsule essential for infection and induced spreading of capsule loss in the biofilm, and tuning tail fiber and capsule levels altered the resistance. Latent infections sustained in the biofilm despite resistance, allowing stable phage-bacteria coexistence. Last, we showed that the resistance exposed vulnerabilities in the biofilm. Our findings indicate that phage lysate plays important roles in shaping phage-biofilm interactions and open more dimensions for the rational design of strategies to counter bacteria with phage. [ABSTRACT FROM AUTHOR]
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- 2024
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4. The emerging links between immunosenescence in innate immune system and neurocryptococcosis.
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Soraci, Luca, Beccacece, Alessia, Princiotto, Maria, Savedra, Edlin Villalta, Gambuzza, Maria Elsa, Aguennouz, M’Hammed, Corsonello, Andrea, Luciani, Filippo, Muglia, Lucia, Filicetti, Elvira, Greco, Giada Ida, Volpentesta, Mara, and Biscetti, Leonardo
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LATENT infection ,OLDER people ,CENTRAL nervous system diseases ,CRYPTOCOCCUS neoformans ,CRYPTOCOCCOSIS - Abstract
Immunosenescence refers to the age-related progressive decline of immune function contributing to the increased susceptibility to infectious diseases in older people. Neurocryptococcosis, an infectious disease of central nervous system (CNS) caused by Cryptococcus neoformans (C. Neoformans) and C. gattii, has been observed with increased frequency in aged people, as result of the reactivation of a latent infection or community acquisition. These opportunistic microorganisms belonging to kingdom of fungi are capable of surviving and replicating within macrophages. Typically, cryptococcus is expelled by vomocytosis, a non-lytic expulsive mechanism also promoted by interferon (IFN)-I, or by cell lysis. However, whereas in a first phase cryptococcal vomocytosis leads to a latent asymptomatic infection confined to the lung, an enhancement in vomocytosis, promoted by IFN-I overproduction, can be deleterious, leading the fungus to reach the blood streamand invade the CNS. Cryptococcus may not be easy to diagnose in older individuals and, if not timely treated, could be potentially lethal. Therefore, this review aims to elucidate the putative causes of the increased incidence of cryptococcal CNS infection in older people discussing in depth the mechanisms of immunosenscence potentially able to predispose to neurocryptococcosis, laying the foundations for future research. A deepest understanding of this relationship could provide new ways to improve the prevention and recognition of neurocryptococcosis in aged frail people, in order to quickly manage pharmacological interventions and to adopt further preventive measures able to reduce the main risk factors. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Applications of Biological Therapy for Latent Infections: Benefits and Risks.
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Zong, Yuan, Kamoi, Koju, Miyagaki, Miki, Zhang, Jing, Yang, Mingming, Zou, Yaru, and Ohno-Matsui, Kyoko
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BIOTHERAPY , *LATENT infection , *COVID-19 , *GRAFT rejection , *DRUG target - Abstract
Biological therapies have revolutionized medical treatment by targeting the key mediators or receptors involved in inflammatory responses, thereby effectively suppressing inflammation and achieving beneficial outcomes. They are more advanced than conventional therapies using corticosteroids and immunosuppressants, offering effective solutions for autoimmune diseases, cancer, transplant rejection, and various infectious diseases, including coronavirus disease 2019. Although they exert low immunosuppressive effects, biological therapies can reactivate specific biological targets associated with infections. This review summarizes the currently available biological therapies and discusses their immunosuppressive mechanisms and clinical applications, highlighting the variations in the types and frequencies of infection recurrence induced by different biological agents. Additionally, this review describes the risk factors associated with various biological agents, thus aiding clinicians in selecting the most appropriate biological therapy. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Occurrence of blueberry virus L in Japan and its aphid transmission and pathogenicity in highbush blueberry.
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Isogai, Masamichi, Yamamura, Misaki, Sakamoto, Hijiri, Yaegashi, Hajime, and Watanabe, Manabu
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VACCINIUM corymbosum , *COTTON aphid , *LATENT infection , *NUCLEOTIDE sequence , *APHIDS - Abstract
This is the first report of the occurrence of blueberry virus L (BlVL) in Japan and the complete nucleotide sequence of a Japanese isolate. BlVL was detected using reverse transcription-polymerase chain reaction in 35 of 52 highbush blueberry shrubs at Iwate University Research Farm, Japan, and in aphids (Aphis gossypii) on a BlVL-infected blueberry shrub. In the aphid transmission test of BlVL, the aphids transmitted the virus to uninfected blueberry bushes. No symptoms were observed in shrubs infected with the virus by aphid inoculation or by graft inoculation, suggesting that BlVL causes latent infection in highbush blueberry. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Origins of the problematic E in SEIR epidemic models.
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Burke, Donald S.
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EPIDEMIOLOGICAL models , *PUBLIC health , *COMMUNICABLE diseases , *ENGLISH language , *TERMS & phrases - Abstract
During the COVID-19 pandemic, over one thousand papers were published on "Susceptible- Exposed-Infectious-Removed" (SEIR) epidemic computational models. The English word "exposed" in its vernacular and public health usage means a state of having been in contact with an infectious individual, but not necessarily infected. In contrast, the term "exposed" in SEIR modeling usage typically stands for a state of already being infected but not yet being infectious to others, a state more properly termed "latently infected." In public health language, "exposed" means possibly infected, yet in SEIR modeling language, "exposed" means already infected. This paper retraces the conceptual and mathematical origins of this terminological disconnect and concludes that epidemic modelers should consider using the "SLIR" notational short-hand (L for Latent) instead of SEIR. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Integration of mathematical modeling and target‐based application of biocontrol agents for the control of Botrytis cinerea in vineyards.
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Altieri, Valeria, Rossi, Vittorio, and Fedele, Giorgia
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MOLD control ,LATENT infection ,BOTRYTIS cinerea ,FUNGICIDES ,PREDICTION models - Abstract
BACKGROUND: Biocontrol agents (BCAs) are alternatives to synthetic fungicides with low risk to the environment and human health. Although several studies on the biocontrol of gray mold in vineyards have been performed, it is necessary to improve the usage of BCAs in fields conditions. Therefore, in the present study, BCAs were used both in calendar‐based [based on four growth stages (GSs), i.e., flowering, pre‐bunch closure, veraison, and before harvest] and predictive model‐based strategies (only when Botrytis cinerea infection risk was predicted by the model). The BCAs applied during the seasons were selected considering the grapevine GSs. Treatments performed with BCAs were compared with synthetic fungicide treatments and an untreated control. The trials were conducted in three experimental vineyards with four epidemics. To evaluate the level of gray mold control of each treatment, disease severity was assessed at harvest and the presence of latent infection was evaluated. RESULTS: The integrative use of the predictive model and BCAs provided satisfactory levels of gray mold control, with gray mold severity levels significantly lower (P < 0.001) than those of the untreated control, which had severity values (< 7%) similar to those observed with synthetic fungicides following both calendar and model‐based strategies. CONCLUSIONS: The integrative use of the predictive model and BCAs represents a valid alternative to conventional methods of gray mold control in vineyards, with more than 75% reduction in fungicide usage. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]
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- 2024
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9. A review of HSV pathogenesis, vaccine development, and advanced applications.
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Bai, Lan, Xu, Jiuzhi, Zeng, Linghui, Zhang, Long, and Zhou, Fangfang
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HERPES simplex virus ,ONCOLYTIC virotherapy ,LATENT infection ,GENETIC load ,VACCINE development - Abstract
Herpes simplex virus (HSV), an epidemic human pathogen threatening global public health, gains notoriety for its complex pathogenesis that encompasses lytic infection of mucosal cells, latent infection within neurons, and periodic reactivation. This intricate interplay, coupled with HSV's sophisticated immune evasion strategies, gives rise to various diseases, including genital lesions, neonatal encephalitis, and cancer. Despite more than 70 years of relentless research, an effective preventive or therapeutic vaccine against HSV has yet to emerge, primarily due to the limited understanding of virus-host interactions, which in turn impedes the identification of effective vaccine targets. However, HSV's unique pathological features, including its substantial genetic load capacity, high replicability, transmissibility, and neurotropism, render it a promising candidate for various applications, spanning oncolytic virotherapy, gene and immune therapies, and even as an imaging tracer in neuroscience. In this review, we comprehensively update recent breakthroughs in HSV pathogenesis and immune evasion, critically summarize the progress made in vaccine candidate development, and discuss the multifaceted applications of HSV as a biological tool. Importantly, we highlight both success and challenges, emphasizing the critical need for intensified research into HSV, with the aim of providing deeper insights that can not only advance HSV treatment strategies but also broaden its application horizons. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Latent toxoplasmosis, Cytomegalovirus, and Herpes Simplex Virus infections and risk of motorcycle accidents: A case-control study in a county with a high rate of motorcycle injuries in Iran.
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Rayatdoost, Esmail, Chegin, Mahdi, Taghipour, Ali, Shadmand, Enayat, Rezaei, Fatemeh, Falahi, Shahab, Kenarkoohi, Azra, Badri, Milad, Solhjoo, Kavous, and Abdoli, Amir
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LATENT infection , *HERPES simplex virus , *ENZYME-linked immunosorbent assay , *MOTORCYCLING injuries , *CYTOMEGALOVIRUS diseases , *MOTORCYCLING accidents - Abstract
Background: Road traffic injuries (RTIs) are among the most important issues worldwide. Several studies reported that infection with the neurotropic parasite Toxoplasma gondii (T. gondii) increased the risk of car accidents. In this study, our objective was to investigate the possible associations among latent T. gondii, Cytomegalovirus (CMV), and Herpes Simplex Virus (HSV) infections with the risk of motorcycle accidents in Jahrom (Fars Province), which is a county with a high rate of motorcycle accidents in Iran. Methods: In the setting of a case-control study; 176 motorcyclist men, including 88 survivors of motorcycle accidents and 88 motorcyclist without accidents, were considered as case and control groups, respectively. Rates of latent infections with T. gondii, CMV, and HSV were assessed by an enzyme-linked immunosorbent assay (ELISA). Results: Eleven of 88 (12.5%) in the case group and 22 of 88 (25.0%) in controls were positive for anti-T. gondii IgG antibodies, this difference was statistically significant (OR = 0.42; CI: 0.19–0.95, p = 0.03). The general seroprevalence of CMV (94.3% in the case group vs. 87.5% in the control group, OR = 2.37; CI: 0.78–7.13, p = 0.12) and HSV (63.6% in the case group vs. 62.5% in the control group, OR = 1.05; CI: 0.57–1.94, p = 0.87) were not significantly different between the case and control groups. Conclusions: Although latent toxoplasmosis has been associated with traffic accidents in recent reports, we found a negative association between latent toxoplasmosis and motorcycle accidents among survivors of these accidents. As such, latent CMV and HSV infections did not differ significantly between the cases compared to the control groups. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Treatment of psoriasis with biologic and non‐biologic targeted therapies in patients with latent tuberculosis infection or at risk for tuberculosis disease progression: Recommendations from a SPIN‐FRT expert consensus.
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Torres, T., Brembilla, N. C., Langley, R. G., Warren, R. B., Thaçi, D., Kolios, A. G. A., Prinz, J. C., Londono‐Garcia, A., Nast, A., Santin, M., Goletti, D., Abreu, M., Spuls, P., Boehncke, W. H., and Puig, L.
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LATENT tuberculosis , *LATENT infection , *MYCOBACTERIUM tuberculosis , *CLINICAL trials , *DRUG toxicity - Abstract
Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a significant global health problem. In immunocompetent individuals, the microorganism can remain in a latent, non‐contagious form, however, it may become active under conditions of immunosuppression. Tumour necrosis factor (TNF) inhibitors, which are frequently used for the management of immune‐mediated disorders like psoriasis, have been associated with a significantly increased risk of reactivating latent TB. Consequently, international guidelines recommend TB screening and preventive treatment before starting anti‐TNF therapy. These recommendations have extended to IL‐12/23, IL‐17, IL‐23 and TYK2 inhibitors under a caution principle, despite their different mechanisms of action. However, current evidence suggests that some of these agents are arguably not associated with an increased risk of TB reactivation or development of TB disease after infection, which calls for a critical reassessment of these guidelines. We have conducted a literature search evaluating the risk of TB reactivation associated with these innovative therapies, integrating findings from both randomized clinical trials and real‐world evidence. The identified evidence is limited but the low number of identified cases of reactivation with IL‐17 and IL‐23 inhibitors prompts reconsidering the need for preventive treatment for latent TB in all cases, regardless of biologic class or individual patient's risk of TB reactivation or drug toxicity. This review, along with the clinical insight of a panel of experts on behalf of the SPIN‐FRT, led to the development of these consensus recommendations for managing psoriasis treatment in patients with latent TB infection or at risk of TB infection, who are receiving or are intended to receive biologic and non‐biologic targeted therapies. These recommendations highlight the need for updates to the existing guidelines, aiming to provide a more differentiated approach that reflects the evolving landscape of psoriasis treatment and its implications for TB management. [ABSTRACT FROM AUTHOR]
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- 2024
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12. Human Herpesvirus 6—A Rare Aetiologic Agent for CNS Infections in Immunocompetent Individuals or an Underestimation?
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Ganea, Oana Alexandra, Tilișcan, Cătălin, Streinu-Cercel, Anca, Pițigoi, Daniela, Drăgănescu, Anca Cristina, Lazar, Mihai, Mihai, Nicoleta, Florea, Dragoș, Aramă, Sorin Ștefan, and Aramă, Victoria
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HUMAN herpesvirus-6 , *LATENT infection , *INFECTION , *DIAGNOSTIC use of polymerase chain reaction , *CENTRAL nervous system - Abstract
Background: Human herpesvirus 6 (HHV-6) is considered a ubiquitous virus, with many countries reporting a seroprevalence of more than 80–90% among the general population. However, this virus is unique among herpesviruses in its ability to integrate into the genetic material of the host's cells. Thus, there are three ways by which HHV-6 can cause an active infection–primary infection, reactivation of a latent acquired infection, or activation of iciHHV-6 (inherited chromosomally integrated HHV-6). Whole blood quantitative polymerase chain reaction (qPCR) is very useful in distinguishing between iciHHV-6 and primary infection/reactivation. Our aim is to assess the role of HHV-6 in the aetiology of central nervous system (CNS) infections in adults and children, to describe all HHV-6-positive cases in an attempt to determine the susceptible population and to identify potential risk factors that can be linked to HHV-6 meningoencephalitis. Methods: We performed a retrospective study involving patients that were admitted to Prof. Dr. Matei Bals National Institute of Infectious Diseases, Bucharest, Romania, with a diagnosis of meningitis or encephalitis. We only selected the clinical records of patients that had a multiplex PCR Biofire® FilmArray® meningitis/encephalitis panel. Results: We report a 5% HHV-6 positivity in the cerebrospinal fluid (CSF) of patients with CNS infections tested with a commercial multiplex PCR M/E (meningitis/encephalitis) panel. Additionally, 2% to 4% of the total study population (n = 100) had active HHV-6 infections, which denotes 40 to 80% of the HHV-6-positive samples. We did not observe any statistically significant correlation between HHV-6 positivity in the CSF and variables such as age, sex, or comorbidities, including obesity, diabetes, hypertension, immunosuppression, or oncologic disease. Therefore, no risk factors could be linked with HHV-6 positivity in the CSF. Conclusions: although multiplex qualitative PCR is highly useful for providing rapid results and identifying nearly every pathogen that can cause meningitis/encephalitis, we have to be aware of this type of test's limitations. All patients with HHV-6 detectable in their CSF via a multiplex PCR test should also undergo qPCR testing from both CSF and blood to prevent over-diagnosing HHV-6 CNS infections, to avoid unnecessary antiviral treatments, and ensure the accurate identification of the true diagnosis. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Factors associated with incomplete tuberculosis preventive treatment: a retrospective analysis of six-years programmatic data in Cambodia.
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An, Yom and Khun, Kim Eam
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LATENT infection , *MANAGEMENT information systems , *HEALTH facilities , *INFORMATION resources management , *ISONIAZID - Abstract
Tuberculosis (TB) preventive treatment (TPT) effectively prevents the progression from TB infection to TB disease. This study explores factors associated with TPT non-completion in Cambodia using 6-years programmatic data (2018–2023) retrieved from the TB Management Information System (TB-MIS). Out of 14,262 individuals with latent TB infection (LTBI) initiated with TPT, 299 (2.1%) did not complete the treatment. Individuals aged between 15–24 and 25–34 years old were more likely to not complete the treatment compared to those aged < 5 years old, with aOR = 1.7, p = 0.034 and aOR = 2.1, p = 0.003, respectively. Individuals initiated with 3-month daily Rifampicin and Isoniazid (3RH) or with 6-month daily Isoniazid (6H) were more likely to not complete the treatment compared to those initiated with 3-month weekly Isoniazid and Rifapentine (3HP), with aOR = 2.6, p < 0.001 and aOR = 7, p < 0.001, respectively. Those who began TPT at referral hospitals were nearly twice as likely to not complete the treatment compared to those who started the treatment at health centers (aOR = 1.95, p = 0.003). To improve TPT completion, strengthen the treatment follow-up among those aged between 15 and 34 years old and initiated TPT at referral hospitals should be prioritized. The national TB program should consider 3HP the first choice of treatment. [ABSTRACT FROM AUTHOR]
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- 2024
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14. Grapevine Pinot gris virus spreads in infected vineyards: latent infections have no direct impact on grape production.
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Messmer, Noemi, Bohnert, Patricia, Askani, Lars, Schumacher, Stefan, Voegele, Ralf T., and Fuchs, René
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LATENT infection , *PINOT gris , *CREDIT spread , *PLANT performance , *VIRAL transmission - Abstract
Background: Grapevine Pinot gris virus (GPGV) infects grapevines worldwide and causes symptoms such as chlorotic mottling and deformations on leaves, stunted shoots and short panicles, or none of these symptoms if it appears as latent infection. So far, the consequences of GPGV infections for winegrowers are difficult to assess since important information such as plant performance at different GPGV infection levels and symptom expression are not fully clarified. Methods: In order to investigate the course of GPGV spread, annual visual evaluations and ELISA tests were conducted over 3–4 consecutive years in four GPGV-infected vineyards in southern Germany: GEM, HEC, NIM, and REI. The program PATCHY was used to analyze spatial disease patterns. Sanger sequencing was used to determine virus isolates in vines at different GPGV infection levels, to test their respective influence on symptom expression. Yield and GrapeScan (FTIR) analyses were conducted to test the impact of different GPGV infection levels and isolates on fruit quantity and quality. Results: GPGV infections significantly increased in all four vineyards (GEM 22–32%, HEC 50–99%, NIM 83–90%, REI 56–76%) with significant spreading patterns across and along rows. Specific symptom progression patterns were not observed. According to our results, the virus isolate has an influence on whether symptoms develop during a GPGV infection. While yield analyses revealed that yield losses only occur in symptomatic vines and range from 13 to 96% depending on the severity of symptoms, latent infections have no impact on grape production. No relevant effects of GPGV infections on must quality were observed. Conclusions: Secondary spread of GPGV was observed in all vineyards monitored, indicating vector-borne transmission that is likely to be accelerated by human viticultural management. GPGV should be further monitored to prevent the accumulation of detrimental symptomatic isolates. The results of this study can be used to assess the risk of GPGV to viticulture and should be considered when developing management strategies against the virus. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Decreased T‐cell response against latent cytomegalovirus infection does not correlate with anti‐IFN autoantibodies in patients with APECED.
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Hetemäki, Iivo, Heikkilä, Nelli, Peterson, Pärt, Kekäläinen, Eliisa, Willcox, Nick, Anette S. B., Wolff, Jarva, Hanna, and Arstila, T Petteri
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TYPE I interferons , *LATENT infection , *CYTOMEGALOVIRUS diseases , *FALSE positive error , *VIRUS diseases - Abstract
Autoimmune polyendocrinopathy‐candidiasis‐ectodermal dystrophy (APECED) is an inborn error of immunity affecting both multiple endocrine organs and susceptibility to candidiasis, each with an autoimmune basis. Recently, high titer neutralizing anti‐type I interferon (IFN) autoantibodies have been linked with increased severity of SARS‐CoV‐2 and varicella zoster virus infections in APECED patients. Examining immunity against cytomegalovirus (CMV), we found a higher prevalence of anti‐CMV IgG antibodies in patients with APECED (N = 19) than in 44 healthy controls (90% vs 64%, p = 0.04); the similar difference in their IgG levels did not achieve significance (95 ± 74 vs 64 ± 35 IU/mL, ns.). In contrast, the frequency of CMV‐specific T cells was lower (804 ± 718/million vs 1591 ± 972/million PBMC p = 0.03). We saw no correlations between levels of anti‐CMV IgG and anti‐IFN antibodies in APECED patients or in a separate cohort of patients with thymoma (n = 70), over 60% of whom also had anti‐IFN antibodies. Our results suggest a dysregulated response to CMV in APECED patients and highlight immunodeficiency to viral infections as part of the disease spectrum. [ABSTRACT FROM AUTHOR]
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- 2024
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16. Natural Products from Brazilian Biodiversity Explored as Anti-EBV Drug Candidates: <italic>In-Silico</italic> Database Mining, Docking Computations, Molecular Dynamics and DFT Calculations.
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Hassan, Alaa M. A., Sidhom, Peter A., Mekhemer, Gamal A. H., El-Tayeb, Mohamed A., Hegazy, Mohamed-Elamir F., and Ibrahim, Mahmoud A. A.
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ONCOGENIC DNA viruses , *LATENT infection , *NATURAL products , *BINDING energy , *DATABASES - Abstract
A DNA tumor virus called Epstein–Barr virus (EBV) is the cause of 1–2% of human cancers. EBV-associated carcinogenesis is caused by a persistent latent infection. The shortage of antiviral medications or vaccinations to control the virus led to a significant percentage of critically sickness individuals needing to be hospitalized. In the absence of an effective vaccine and approved drug, there is an immediate need for treatments that can combat EBV infection. Epstein–Barr nuclear antigen 1 (EBNA1) is continually expressed in all malignancies linked to EBV; it is a desirable target for curative interference. Herein, natural product compounds from the Nuclei of Bioassays, Ecophysiology and Biosynthesis of Natural Products (NuBBE) database were mined to identify potent EBNA1 inhibitors. The performance of the molecular docking technique was initially assessed in expecting the ligand-target binding pose according to the available experimental data. On the basis of the estimated docking protocol, the NuBBE database was virtually screened toward the EBNA1 protein, and the natural compounds with binding scores less than KWG (calc. -7.8 kcal/mol) were subjected to molecular dynamics (MD) simulations followed by binding energy (ΔGbinding) calculation using MM/GBSA approach. Based on binding energy computations, NuBBE1460 revealed superior ΔGbinding with a value of −36.2 kcal/mol, compared to KWG (calc. -32.4 kcal/mol). Post-MD analyses displayed a high steadiness of NuBBE1460 within the EBNA1 protein binding pocket. Furthermore, the physicochemical, pharmacokinetic and toxicity features of the identified compound were predicted, demonstrating high degrees of its oral bioavailability. The energetical and geometrical properties of NuBBE1460 were calculated using the DFT method. Conclusively, this study offers NuBBE1460 obtained from natural sources as a lead EBNA1 inhibitor for future investigation and development as a therapeutic for EBV. [ABSTRACT FROM AUTHOR]
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- 2024
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17. Drug Persistence and Incidence of Active Tuberculosis of Tumor Necrosis Factor Alpha Inhibitors Versus Tocilizumab as the First-Line Biological Treatment in Patients with Rheumatoid Arthritis: A Nationwide Population-Based Retrospective Cohort Analysis.
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So, Min Wook, Kim, A-Ran, and Lee, Seung-Geun
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TUMOR necrosis factors , *RHEUMATOID arthritis , *TOCILIZUMAB , *LATENT infection , *COHORT analysis , *OPPORTUNISTIC infections - Abstract
Introduction: Drug persistence may be a surrogate marker that reflects both long-term efficacy and safety in clinical settings, and tuberculosis (TB) is considered as one of the most important opportunistic infections after the biological treatment in rheumatoid arthritis (RA). We aimed to compare drug persistence and incidence of TB between tumor necrosis factor alpha (TNFα) inhibitors and tocilizumab in patients with RA using data from the Korean Health Insurance Review and Assessment Service database. Methods: In this analysis, 5449 patients with RA who started TNFα inhibitors, such as adalimumab, etanercept, infliximab, and golimumab or tocilizumab, as the first-line biological therapy between January 2014 and December 2017 were analyzed and followed up until December 2019. Drug persistence was defined as the duration from initiation to first discontinuation, and TB was defined as the prescription of > 2 anti-TB medications after the initiation of biologics. Results: TNFα inhibitors and tocilizumab were prescribed in 4202 (adalimumab, 1413; etanercept, 1100; infliximab, 769; golimumab 920) and 1247 patients with RA, respectively. During the analysis period, 2090 (49.7%) and 477 (38.3%) patients with RA discontinued TNFα inhibitors and tocilizumab, respectively, and 42 patients with RA developed TB (TNFα inhibitors, 33; tocilizumab, 9). After adjustment for confounding factors, TNFα inhibitors were significantly associated with a higher risk of discontinuation compared with tocilizumab (hazard ratio (HR) 1.63, p < 0.001). In subgroup analysis, all types of TNFα inhibitors, except for infliximab, demonstrated a significantly lower persistence rate compared with tocilizumab. There was no significant difference in TB incidence between tocilizumab and TNFα inhibitors. In subgroup analysis, infliximab has a significantly higher risk of TB compared with tocilizumab (HR 2.84, p = 0.02). Conclusion: In this analysis, tocilizumab had longer persistence than TNFα inhibitors with a similar incidence of TB. Our analysis has limitations: (1) The HIRA database lacks clinical details like disease activity and joint damage extent, potentially influencing the analysis results. (2) Reasons for discontinuing biological agents were not available. (3) TB diagnoses may be inaccurate because of missing microbiological results. (4) We did not analyze the impact of treating latent TB infection on TB development post-biological treatment, despite mandatory screening in Korea. [ABSTRACT FROM AUTHOR]
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- 2024
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18. PM 7/90 (2) Anisogramma anomala.
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HAZEL , *NUCLEIC acids , *DNA analysis , *NUCLEIC acid isolation methods , *LATENT infection , *DNA primers - Abstract
This document is a diagnostic protocol for Anisogramma anomala, a pathogen that causes eastern filbert blight on European hazelnut trees. It provides information on identifying and detecting the pathogen, including its symptoms and characteristics. The document includes molecular tests for confirmation in critical cases and emphasizes the importance of early detection. It also provides guidance on reporting and documentation, as well as contact information for further information. The appendices provide instructions for isolating the organism and describe the media used for its growth. The document also includes instructions for conducting a real-time PCR test to detect A. anomala, with information on controls, interpretation of results, and performance characteristics. The test has been validated and shown to have high sensitivity and specificity. [Extracted from the article]
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- 2024
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19. Ten missteps in the management of inflammatory bowel disease in Asia: An expert report by the Asian Pacific Association of Gastroenterology Working Group on Inflammatory Bowel Disease.
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Ahuja, Vineet, Hilmi, Ida, Ye, Byong Duk, Ling, Khoon Lin, Ng, Siew C., Leong, Rupert W., Kumar, Peeyush, Khoo, Xin Hui, Makharia, Govind K., Sollano, Jose, Pisespongsa, Pises, Mustaffa, Nazri, Banerjee, Rupa, Leow, Alex Hwong‐Ruey, Raja Ali, Raja Affendi, Chuah, Sai Wei, Palaniappan, Shanthi, Ooi, Choon Jin, and Leung, Wai K.
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CROHN'S disease , *INFLAMMATORY bowel diseases , *LATENT infection , *ULCERATIVE colitis , *PHYSICIANS - Abstract
Inflammatory bowel disease (IBD) is rapidly emerging in the Asia Pacific region. However, there are many challenges in the diagnosis and management of this condition. The Asian Pacific Association of Gastroenterology (APAGE) Working Group on IBD conducted a round table meeting to identify 10 common mistakes in the management of IBD in Asia. To summarize, many physicians still over rely on a definitive histological diagnosis before starting treatment and do not fully establish disease extent such as perianal and proximal gastrointestinal involvement in Crohn's disease (CD) or extent of involvement in ulcerative colitis (UC). It is also essential to actively look for evidence of extra‐intestinal manifestations, which may influence choice of therapy. In terms of conventional therapy, underuse of topical 5 aminosalicylates (5‐ASAs) in UC and inappropriate dosing of corticosteroids are also important considerations. Acute severe UC remains a life‐threatening condition and delay in starting rescue therapy after inadequate response to intravenous steroids is still common. Anti‐tumor necrosis factors should be considered first line in all cases of complex perianal fistulizing CD. Most patients with IBD are on potent immunosuppressive therapy and should be screened for latent infections and offered vaccinations according to guidelines. Under‐recognition and management of significant complications such as anemia, osteoporosis, malnutrition, and thromboembolism should also be addressed. Colonoscopy is still not properly performed for dysplasia/cancer surveillance and for evaluating post‐op recurrence of CD. Another common misstep is inappropriate withdrawal of medications during pregnancy leading to increased complications for the mother and the newborn. [ABSTRACT FROM AUTHOR]
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- 2024
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20. Tuberculosis among children visiting friends & relatives.
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Perez-Porcuna, Tomas M, Noguera-Julian, Antoni, Riera-Bosch, Maria Teresa, Macià-Rieradevall, Esperança, Santos-Santiago, José, Pujol, Maria Àngels Rifà, Eril, Maria, Aulet-Molist, Lídia, Padilla-Esteba, Emma, Tórtola, Maria Teresa, Prat, Jordi Gómez i, Bastarras, Anna Vilamala, Rebull-Fatsini, Josep Sebastià, Papaleo, Andrea, Rius-Gordillo, Neus, Gonçalves, Alessandra Q, Naranjo-Orihuela, Àngels, Urgelles, Marta, García-Lerín, Mónica G, and Jimenez-Lladser, Gemma
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LATENT infection , *SMOKING , *CHILDREN of immigrants , *TOBACCO smoke , *TUBERCULIN test - Abstract
Background Most paediatric tuberculosis (TB) cases in low-TB-incidence countries involve children born to migrant families. This may be partially explained by trips to their countries of origin for visiting friends and relatives (VFR). We aimed to estimate the risk of latent TB infection (LTBI) and TB in children VFR. Methods We conducted a prospective multicentric observational study in Catalonia (Spain) from June 2017 to December 2019. We enrolled children aged < 15 years with a negative tuberculin skin test (TST) at baseline and at least one parent from a high-TB-incidence country, and who had travelled to their parent's birth country for ≥21 days. TST and QuantiFERON-TB Gold Plus (QFT-Plus) were performed within 8–12 weeks post-return. LTBI was defined as a TST ≥5 mm and/or a positive QFT-Plus. Results Five hundred children completed the study, equivalent to 78.2 person-years of follow-up (PYFU). Thirteen children (2.6%) were diagnosed with LTBI (16.6/per100 PYFU, 95%CI = 8.8–28.5), including two cases (0.4%) of TB (2.5/per100 PYFU, 95%CI = 0.3–9.3). LTBI incidence rates remained high after excluding BCG-vaccinated children (9.7/per100 PYFU, 95%CI = 3.9–20.0). Household tobacco smoke exposure was associated with LTBI (aOR = 3.9, 95%CI = 1.1–13.3). Conclusions The risk of LTBI in children VFR in high-TB-incidence countries may equal, or perhaps even exceed, the infection risk of the native population. The primary associated risk factor was the presence of smokers in the household. Furthermore, the incidence rate of active TB largely surpassed that of the countries visited. Children VFR in high-TB-incidence countries should be targeted for diagnostic and preventive interventions. [ABSTRACT FROM AUTHOR]
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- 2024
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21. Decomposed FDG PET-based phenotypic heterogeneity predicting clinical prognosis and decision-making in temporal lobe epilepsy patients.
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Guo, Kun, Quan, Zhiyong, Li, Guiyu, Li, Baojuan, Kang, Fei, and Wang, Jing
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EPILEPSY , *TEMPORAL lobe epilepsy , *PEOPLE with epilepsy , *LATENT infection , *PROGNOSIS , *HETEROGENEITY - Abstract
Objective: This study utilized a data-driven Bayesian model to automatically identify distinct latent disease factors represented by overlapping glucose metabolism patterns from 18F-Fluorodeoxyglucose PET (18F-FDG PET) to analyze heterogeneity among patients with TLE. Methods: We employed unsupervised machine learning to estimate latent disease factors from 18F-FDG PET scans, representing whole-brain glucose metabolism patterns in seventy patients with TLE. We estimated the extent to which multiple distinct factors were expressed within each participant and analyzed their relevance to epilepsy burden, including seizure onset, duration, and frequency. Additionally, we established a predictive model for clinical prognosis and decision-making. Results: We identified three latent disease factors: hypometabolism in the unilateral temporal lobe and hippocampus (factor 1), hypometabolism in bilateral prefrontal lobes (factor 2), and hypometabolism in bilateral temporal lobes (factor 3), variably co-expressed within each patient. Factor 3 demonstrated the strongest negative correlation with the age of onset and duration (r = − 0.33, − 0.38 respectively, P < 0.05). The supervised classifier, trained on latent disease factors for predicting patient-specific antiepileptic drug (AED) responses, achieved an area under the curve (AUC) of 0.655. For post-surgical seizure outcomes, the AUC was 0.857, and for clinical decision-making, it was 0.965. Conclusions: Decomposing 18F-FDG PET-based phenotypic heterogeneity facilitates individual-level predictions relevant to disease monitoring and personalized therapeutic strategies. [ABSTRACT FROM AUTHOR]
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- 2024
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22. The pre‐transplant evaluation: Considerations for trainees and early career transplant infectious diseases clinician.
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Kumar, Rebecca N., Gorsline, Chelsea A., Rader, Theodore, Boucher, Helen W., Malinis, Maricar, Koff, Alan, and Harris, Courtney E.
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LATENT infection , *MEDICAL education , *TRANSPLANTATION of organs, tissues, etc. , *COMMUNICABLE diseases , *MEDICAL personnel - Abstract
Transplant infectious disease (TID) clinicians are integral to the pre‐transplantation evaluation. Pre‐transplant evaluations allow clinicians to assess risk factors for latent infections and relevant exposures to potential pathogens, address immunizations, and optimize patients' health and understanding of life after transplant. However, there is not a standardized approach to the pre‐transplant evaluation. This article reviews the details of performing successful pre‐transplant evaluations, including updated recommendations on available vaccines and contemporary opinions on marijuana use. This resource can be used for teaching with trainees or for early career TID clinicians. [ABSTRACT FROM AUTHOR]
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- 2024
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23. Motor progression trajectories and risk of mild cognitive impairment in Parkinson's disease: A latent class trajectory model from PPMI cohort.
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Chen, Xi, He, Chentao, Ma, Jianrui, Yang, Rui, Qi, Qi, Gao, Ziqi, Du, Tingyue, Zhang, Piao, Li, Yan, Cai, Mengfei, and Zhang, Yuhu
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PARKINSON'S disease , *PROPORTIONAL hazards models , *MILD cognitive impairment , *PROPENSITY score matching , *LATENT infection - Abstract
Aims: Rare studies have investigated the association between heterogeneity of motor progression and risk of early cognitive impairment in Parkinson's disease (PD). In this study, we aim to identify distinct trajectories of motor progression longitudinally and investigate their impact on predicting mild cognitive impairment (MCI). Methods: A 5‐year cohort including 415 PD patients at baseline was collected from the Parkinson's Progression Markers Initiative. The severity of motor symptoms was evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale part III. The latent class trajectory model and nonlinear mixed‐effects model were used to analyze and delineate the longitudinal changes in motor symptoms. Propensity score matching (PSM) was used to minimize the impact of potential confounders. Cox proportional hazard models were applied to calculate hazard ratios for MCI, and a Kaplan–Meier curve was generated using the occurrence of MCI during the follow‐up as the time‐to‐event. Results: Two latent trajectories were identified: a mild and remitting motor symptoms class (Class 1, 33.01%) and a severe and progressive motor symptom class (Class 2, 66.99%). Patients in Class 2 initially exhibited severe motor symptoms that worsened progressively despite receiving anti‐PD medications. In comparison, patients in Class 1 exhibited milder symptoms that improved following drug therapy and a slower progression. During a 5‐year follow‐up, patients in Class 2 showed a higher risk of developing MCI compared to those in Class 1 before PSM (Log‐Rank 28.58, p < 0.001) and after PSM (Log‐Rank 8.20, p = 0.004). Conclusions: PD patients with severe and progressive motor symptoms are more likely to develop MCI than those with mild and stable motor symptoms. [ABSTRACT FROM AUTHOR]
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- 2024
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24. ORC1 enhances repressive epigenetic modifications on HIV-1 LTR to promote HIV-1 latency.
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Mo Zhou, Tao Yang, Ming Yuan, Xinyu Li, Jieyi Deng, Shiyu Wu, Zhihan Zhong, Yingtong Lin, Wanying Zhang, Baijin Xia, Yating Wu, Lilin Wang, Tao Chen, Ruxin Liu, Ting Pan, Xiancai Ma, Linghua Li, Bingfeng Liu, and Hui Zhang
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REPLICATION factors (Biochemistry) , *HIV , *LATENT infection , *DNA replication , *PROMOTERS (Genetics) - Abstract
The human immunodeficiency virus type 1 (HIV-1) reservoir consists of latently infected cells which present a major obstacle to achieving a functional cure for HIV-1. The formation and maintenance of HIV-1 latency have been extensively studied, and latency-reversing agents (LRAs) that can reactivate latent HIV-1 by targeting the involved host factors are developed; however, their clinical efficacies remain unsatisfactory. Therefore, it is imperative to identify novel targets for more potential candidates or better combinations for LRAs. In this study, we utilized CRISPR affinity purification in situ of regulatory elements system to screen for host factors associated with the HIV-1 long terminal repeat region that could potentially be involved in HIV-1 latency. We successfully identified that origin recognition complex 1 (ORC1), the largest subunit of the origin recognition complex, contributes to HIV-1 latency in addition to its function in DNA replication initiation. Notably, ORC1 is enriched on the HIV-1 promoter and recruits a series of repressive epigenetic elements, including DNMT1 and HDAC1/2, and histone modifiers, such as H3K9me3 and H3K27me3, thereby facilitating the establishment and maintenance of HIV-1 latency. Moreover, the reactivation of latent HIV-1 through ORC1 depletion has been confirmed across various latency cell models and primary CD4+ T cells from people living with HIV-1. Additionally, we comprehensively validated the properties of liquid-liquid phase separation (LLPS) of ORC1 from multiple perspectives and identified the key regions that promote the formation of LLPS. This property is important for the recruitment of ORC1 to the HIV-1 promoter. Collectively, these findings highlight ORC1 as a potential novel target implicated in HIV-1 latency and position it as a promising candidate for the development of novel LRAs. IMPORTANCE Identifying host factors involved in maintaining human immunodeficiency virus type 1 (HIV-1) latency and understanding their mechanisms prepares the groundwork to discover novel targets for HIV-1 latent infection and provides further options for the selection of latency-reversing agents in the “shock” strategy. In this study, we identified a novel role of the DNA replication factor origin recognition complex 1 (ORC1) in maintaining repressive chromatin structures surrounding the HIV-1 promoter region, thereby contributing to HIV-1 latency. This discovery expands our understanding of the non-replicative functions of the ORC complex and provides a potential therapeutic strategy for HIV-1 cure. [ABSTRACT FROM AUTHOR]
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- 2024
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25. MANIFESTAÇÕES NEUROLÓGICAS APÓS PROCEDIMENTO ANESTÉSICO EM CÃO DOMÉSTICO COM CINOMOSE E TOXOPLASMOSE: RELATO DE CASO.
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Alves Santomauro, Rafael, da Silva Marques, Mariana, Javaroni Perri, Leonardo, Santos Balbino, Letícia, Garcia Suhett, Weslem, Aparecido Barreto, Jerry, and Pinto-Ferreira, Fernanda
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LATENT infection ,PREANESTHETIC medication ,FEMALE dogs ,ZOONOSES ,SYMPTOMS - Abstract
Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2024
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26. Exploring the interplay between Kaposi's sarcoma and SARS‐CoV‐2 infection: A case series and systematic review.
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Pietroluongo, Erica, Luciano, Angelo, Peddio, Annarita, Buonaiuto, Roberto, Caltavituro, Aldo, Servetto, Alberto, De Angelis, Carmine, Arpino, Grazia, Palmieri, Giovannella, Veneziani, Bianca Maria, De Placido, Sabino, Bianco, Roberto, De Placido, Pietro, and Giuliano, Mario
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LATENT infection ,KAPOSI'S sarcoma ,VIRUS reactivation ,LYTIC cycle ,ETIOLOGY of diseases - Abstract
Kaposi's sarcoma (KS) is an angio‐proliferative disease with a viral etiology and a multifactorial pathogenesis that results from immune dysfunction. In patients affected by latent viral infections such as herpesviruses, SARS‐CoV‐2 infection may result in lytic cycle reactivation in host cells. A robust immune system response is crucial for eliminating pathogens and resolving both latent and non‐latent viral infections. We report a case series of KS characterized by tumor progression after SARS‐CoV‐2 infection. We performed a systematic literature review of the PubMed/MEDLINE and EMBASE databases. The keyword terms included "SARS‐CoV‐2," "HHV‐8," "Kaposi's sarcoma," "IL‐6," and "COVID‐19." English language restriction was applied. Items not covered by our study were excluded. KS is a complex disease linked to an impaired immune system. Conditions that result in temporary or permanent immunodeficiency can trigger viral reactivation or exacerbate an existing disease. It is feasible that the increase in cytokine levels in COVID‐19 patients, coupled with lymphocyte downregulation and treatment that induces herpesvirus lytic reactivation, may contribute to the progression of KS after SARS‐CoV‐2 infection. These observations suggest that patients with KS should be clinically monitored both during and after SARS‐CoV‐2 infection. Nevertheless, prospective data should be collected to validate this hypothesis and enhance our understanding of the mechanisms implicated in the onset or progression of KS. [ABSTRACT FROM AUTHOR]
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- 2024
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27. The Wide Spectrum of Presentations of Cytomegalovirus Infection in Immunocompetent Hosts: An Exhaustive Narrative Review.
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Schattner, Ami
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HUMAN cytomegalovirus diseases ,CYTOMEGALOVIRUS diseases ,LATENT infection ,CRITICALLY ill patient care ,SKIN diseases - Abstract
CMV is a ubiquitous DNA virus that establishes infection and results in 40–100% seropositivity. Viral replication occurs following an acquired primary infection (or reinfection) or by the reactivation of life-long latency. In immunocompetent patients, CMV infection is mostly asymptomatic or mild and self-limited. However, an extensive review of the literature published up to April 2024 reveals that despite immunocompetence, CMV can cause a very large variety of clinical syndromes in any part of the gastrointestinal tract (the most common pattern), the central or peripheral nervous system, and the eyes, as well as hematological, pulmonary, cardiac, and cutaneous disease. Not uncommonly, more than one system is involved, and though the disease is often self-limited, treatment with intravenous ganciclovir or oral valganciclovir may be required, and in isolated cases, fatalities may occur. Thus, a potential CMV infection should be considered in the differential of myriad syndromes in non-immunocompromised patients. Associated systemic symptoms (fever, sweats, and weight loss), lymphocytosis, and hepatitis are not uncommon and can be a useful clue. Some populations, such as critically ill patients in intensive care, pregnant women, elderly patients, and those with inflammatory bowel disease, may be more susceptible. Moreover, the potential of past, latent CMV infection (i.e., CMV seropositivity) to be associated with significant cardiovascular morbidity and all-cause mortality years later is intriguing and requires further study. All these data indicate the outstanding importance of developing a vaccine against CMV, which hopefully will become available in the foreseeable future. Meanwhile, a solid diagnosis of active CMV infection can be quickly established (or ruled out) by widely available serology tests and PCR amplification, and clinicians in all disciplines need to be more aware of the diverse guises of CMV infection and remember to consider it in any host, including an immunocompetent one. [ABSTRACT FROM AUTHOR]
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- 2024
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28. New genetic biomarkers from transcriptome RNA-sequencing for Mycobacterium tuberculosis complex and Mycobacterium avium complex infections by bioinformatics analysis.
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Jia, Qingjun, Wu, Yifei, Huang, Yinyan, and Bai, Xuexin
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MYCOBACTERIUM avium , *LATENT infection , *MYCOBACTERIAL diseases , *GENE expression , *BACTERIOPHAGES , *MYCOBACTERIUM tuberculosis - Abstract
The study aims to accurately identify differentially expressed genes (DEGs) and biological pathways in mycobacterial infections through bioinformatics for deeper disease understanding. Differentially expressed genes (DEGs) was explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Unique DEGs were submitted on least absolute shrinkage and selection operator (LASSO) regression analysis. 1,057 DEGs from two GSE datasets were identified, which were closely connected with NTM/ latent TB infection (LTBI)/active TB disease (ATB). It was demonstrated that these DEGs are mainly associated with detoxification processes, and virus and bacterial infections. Moreover, the METTL7B gene was the most informative marker for distinguishing LTBI and ATB with an area under the curve (AUC) of 0.983 (95%CI: 0.964 to 1). The significantly upregulated HBA1/2 genes were the most informative marker for distinguishing between individuals of IGRA-HC/NTM and LTBI (P < 0.001). Moreover, the upregulated HBD gene was also differ between IGRA-HC/NTM and ATB (P < 0.001). We have identified gene signatures associated with Mycobacterium infection in whole blood, which could be significant for understanding the molecular mechanisms and diagnosis of NTM, LTBI, or ATB. [ABSTRACT FROM AUTHOR]
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- 2024
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29. Cholera disease dynamics with vaccination control using delay differential equation.
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Singh, Jaskirat Pal, Kumar, Sachin, Akgül, Ali, and Hassani, Murad Khan
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DELAY differential equations , *CHOLERA vaccines , *LATENT infection , *BODIES of water , *INFECTIOUS disease transmission - Abstract
The COVID-19 pandemic came with many setbacks, be it to a country's economy or the global missions of organizations like WHO, UNICEF or GTFCC. One of the setbacks is the rise in cholera cases in developing countries due to the lack of cholera vaccination. This model suggested a solution by introducing another public intervention, such as adding Chlorine to water bodies and vaccination. A novel delay differential model of fractional order was recommended, with two different delays, one representing the latent period of the disease and the other being the delay in adding a disinfectant to the aquatic environment. This model also takes into account the population that will receive a vaccination. This study utilized sensitivity analysis of reproduction number to analytically prove the effectiveness of control measures in preventing the spread of the disease. This analysis provided the mathematical evidence for adding disinfectants in water bodies and inoculating susceptible individuals. The stability of the equilibrium points has been discussed. The existence of stability switching curves is determined. Numerical simulation showed the effect of delay, resulting in fluctuations in some compartments. It also depicted the impact of the order of derivative on the oscillations. [ABSTRACT FROM AUTHOR]
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- 2024
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30. National rollout of a medication safety dashboard to improve testing for latent infections among biologic and targeted synthetic disease‐modifying agent users within the Veterans Health Administration.
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Schmajuk, Gabriela, Ware, Anna, Li, Jing, Tarasovsky, Gary, Shiboski, Stephen, Barton, Jennifer L., Miller, Karla L., Mitchell, Holly A., Dana, Jo, Reiter, Kimberly, Wahl, Elizabeth, Rozenberg‐Ben‐Dror, Karine, Hauser, Ronald G., and Whooley, Mary A.
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LATENT infection , *VETERANS' health , *MEDICAL personnel , *MEDICATION safety , *CHRONIC hepatitis B , *HEPATITIS B , *ELECTRONIC health records - Abstract
Objective Data Sources and Study Setting Study Design Data Collection Methods Principal Findings Conclusions To develop, deploy, and evaluate a national, electronic health record (EHR)‐based dashboard to support safe prescribing of biologic and targeted synthetic disease‐modifying agents (b/tsDMARDs) in the United States Veterans Affairs Healthcare System (VA).We extracted and displayed hepatitis B (HBV), hepatitis C (HCV), and tuberculosis (TB) screening data from the EHR for users of b/tsDMARDs using PowerBI (Microsoft) and deployed the dashboard to VA facilities across the United States in 2022; we observed facilities for 44 weeks post‐deployment.We examined the association between dashboard engagement by healthcare personnel and the percentage of patients with all screenings complete (HBV, HCV, and TB) at the facility level using an interrupted time series. Based on frequency of sessions, facilities were grouped into high‐ and low/none‐engagement categories. We modeled changes in complete screening pre‐ and post‐deployment of the dashboard.All VA facilities were eligible for inclusion; excluded facilities participated in design of the dashboard or had <20 patients receiving b/tsDMARDs. Session counts from facility personnel were captured using PowerBI audit log data. Outcomes were assessed weekly based on EHR data extracted via the dashboard itself.Totally 117 facilities (serving a total of 41,224 Veterans prescribed b/tsDMARDs) were included. Before dashboard deployment, across all facilities, 61.5% of patients had all screenings complete, which improved to 66.3% over the course of the study period. The largest improvement (15 percentage points, 60.3%–75.3%) occurred among facilities with high engagement (post‐intervention difference in outcome between high and low/none‐engagement groups was 0.17 percentage points (pp) per week, 95% confidence interval (0.04 pp, 0.30 pp); p = 0.01).We observed significant improvements in screening for latent infections among facilities with high engagement with the dashboard, compared with those with fewer sessions. [ABSTRACT FROM AUTHOR]
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- 2024
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31. Kv1.3-induced hyperpolarization is required for efficient Kaposi's sarcoma–associated herpesvirus lytic replication.
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Carden, Holli, Harper, Katherine L., Mottram, Timothy J., Manners, Oliver, Allott, Katie L., Dallas, Mark L., Hughes, David J., Lippiat, Jonathan D., Mankouri, Jamel, and Whitehouse, Adrian
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KAPOSI'S sarcoma-associated herpesvirus ,POTASSIUM channels ,B cells ,T cells ,KAPOSI'S sarcoma ,GENE silencing ,LATENT infection ,GENETIC transcription - Abstract
Kaposi's sarcoma–associated herpesvirus (KSHV) is an oncogenic herpesvirus that is linked directly to the development of Kaposi's sarcoma. KSHV establishes a latent infection in B cells, which can be reactivated to initiate lytic replication, producing infectious virions. Using pharmacological and genetic silencing approaches, we showed that the voltage-gated K
+ channel Kv 1.3 in B cells enhanced KSHV lytic replication. The KSHV replication and transcription activator (RTA) protein increased the abundance of Kv 1.3 and led to enhanced K+ channel activity and hyperpolarization of the B cell membrane. Enhanced Kv 1.3 activity promoted intracellular Ca2+ influx, leading to the Ca2+ -driven nuclear localization of KSHV RTA and host nuclear factor of activated T cells (NFAT) proteins and subsequently increased the expression of NFAT1 target genes. KSHV lytic replication and infectious virion production were inhibited by Kv 1.3 blockers or silencing. These findings highlight Kv 1.3 as a druggable host factor that is key to the successful completion of KSHV lytic replication. Editor's summary: Kaposi's sarcoma is driven by Kaposi's sarcoma–associated herpesvirus (KSHV), which preferentially infects B cells. Carden et al. identified a role for the voltage-gated K+ channel Kv 1.3 in B cells in the lytic phase of KSHV, during which active viral replication occurs. KSHV increased the abundance and activity of Kv 1.3 channels during lytic replication. Overexpression of the KSHV-encoded early protein RTA was sufficient to induce the transcription of Kv 1.3-encoding mRNA. Kv 1.3 maintained a hyperpolarized membrane potential that allowed Ca2+ influx, which was required for KSHV lytic replication. These results suggest that Kv 1.3 is a potential target in treating KSHV-driven malignancies. —Amy E. Baek [ABSTRACT FROM AUTHOR]- Published
- 2024
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32. Thyroid tuberculosis mimicking multinodular goiter: a case report.
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Kindie, Endeshaw Asaye, Belachew, Tigist Hailu, Habte, Lidetu Temeche, Abera, Samuel Addisu, Dejen, Addisu Minaye, Abebe, Sileshi Ayele, and Molla, Yohannis Derbew
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HIV infections , *TUBERCULOSIS , *LATENT infection , *THYROID cancer , *GOITER , *MYCOBACTERIUM tuberculosis , *SPINAL tuberculosis - Abstract
Background: Mycobacterium tuberculosis is the second most common infectious cause of death in adults worldwide. The ability of this organism to efficiently establish latent infection has enabled it to spread to nearly one-third of individuals worldwide. Approximately 8 million new cases of active tuberculosis disease occur each year, leading to about 1.7 million deaths. The disease incidence is magnified by the concurrent epidemic of human immunodeficiency virus infection. A total of 1.3 million people died from tuberculosis in 2022. In 2022, an estimated 10.6 million people fell ill with tuberculosis worldwide, including 5.8 million men, 3.5 million women, and 1.3 million children. We report a case of thyroid tuberculosis presenting as multinodular goiter. Neck ultrasound was done and revealed abscess collection on the background of multinodular colloid goiter. The diagnosis of thyroid tuberculosis was confirmed by a positive GeneXpert of the pus sample and the presence of extensive caseous necrosis on cytopathology examination. Furthermore, anterior neck swelling may provide a diagnostic challenge by clinically mimicking multinodular goiter or thyroid neoplasms. Owing to its rarity and its tendency to pose a clinical diagnostic challenge, we decided to report it. Case presentation: A 60-year-old retired female Ethiopian high-school teacher presented to University of Gondar Hospital, Gondar, Ethiopia with firm, nontender multinodular anterior neck swelling measuring at largest 2 × 3 cm that moves with swallowing. GeneXpert of the pus sample and cytopathology examination confirmed the diagnosis of thyroid tuberculosis, and the patient was started on 2 rifampicin−ethambutol−isoniazid−pyrazinamide/4 rifampicin−isoniazid 3 tablets by mouth/day, which is defined as the preferred first-line anti-tuberculosis regimen in Ethiopia, and pyridoxine 50 mg by mouth per day for 6 months. Since then, she has been followed with regular liver function tests. The patient has shown a smooth course with no significant adverse effects encountered. Currently, the patient has completed her anti-tuberculosis treatment and is doing well. Conclusion: In the clinical evaluation of a patient with anterior neck swelling, tuberculosis must be considered as a differential diagnosis in subjects from endemic areas for early diagnostic workup and management. [ABSTRACT FROM AUTHOR]
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- 2024
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33. Suppression of host gene expression is associated with latent TB infection: a possible diagnostic biomarker.
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Nakiboneka, Ritah, Margaritella, Nicolò, Nyirenda, Tonney, Chaima, David, Walbaum, Natasha, Musisi, Emmanuel, Tionge, Sikwese, Msosa, Takondwa, Nliwasa, Marriott, Msefula, Chisomo L., Sloan, Derek, and Sabiiti, Wilber
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LATENT infection , *GENE silencing , *INTERFERON gamma release tests , *GENE expression , *BIOMARKERS - Abstract
The World Health Organization End TB strategy aims for a 90% reduction of tuberculosis (TB) incidence by 2035. Systematic testing and treatment of latent TB infection (LTBI) among contacts of active TB patients is recommended as one of the ways to curtail TB incidence. However, there is a shortage of tools to accurately diagnose LTBI. We assessed the appropriateness of whole blood host transcriptomic markers (TM) to diagnose LTBI among household contacts of bacteriologically confirmed index cases compared to HIV negative healthy controls (HC). QuantiFERON-TB Gold Plus Interferon gamma release assay (IGRA) and reverse-transcriptase quantitative PCR were used to determine LTBI and quantify TM expression respectively. Association between TM expression and LTBI was evaluated by logistic regression modelling. A total of 100 participants, 49 TB exposed (TBEx) household contacts and 51 HC, were enrolled. Twenty-five (51%) TBEx individuals tested positive by IGRA, and were denoted as LTBI individuals, and 37 (72.5%) HC were IGRA-negative. Expression of 11 evaluated TM was significantly suppressed among LTBI compared to HC. Out of the 11 TM, ZNF296 and KLF2 expression were strongly associated with LTBI and successfully differentiated LTBI from HC. Paradoxically, 21 (49%) TBEx participants who tested IGRA negative exhibited the same pattern of suppressed TM expression as IGRA positive (LTBI-confirmed individuals). Results suggest that suppression of gene expression underlies LTBI and may be a more sensitive diagnostic biomarker than standard-of-care IGRA. [ABSTRACT FROM AUTHOR]
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- 2024
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34. Predicting symptom severity in PSTVd‐infected tomato plants using the PSTVd genome sequence.
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Sun, Jianqiang and Matsushita, Yosuke
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PLANT gene silencing , *AGRICULTURE , *HOST plants , *PLANT breeding , *LATENT infection , *PLANT genomes , *TOMATOES , *POTATOES - Abstract
Viroids, one of the smallest known infectious agents, induce symptoms of varying severity, ranging from latent to severe, based on the combination of viroid isolates and host plant species. Because viroids are transmissible between plant species, asymptomatic viroid‐infected plants may serve as latent sources of infection for other species that could exhibit severe symptoms, occasionally leading to agricultural and economic losses. Therefore, predicting the symptoms induced by viroids in host plants without biological experiments could remarkably enhance control measures against viroid damage. Here, we developed an algorithm using unsupervised machine learning to predict the severity of disease symptoms caused by viroids (e.g., potato spindle tuber viroid; PSTVd) in host plants (e.g., tomato). This algorithm, mimicking the RNA silencing mechanism thought to be linked to viroid pathogenicity, requires only the genome sequences of the viroids and host plants. It involves three steps: alignment of synthetic short sequences of the viroids to the host plant genome, calculation of the alignment coverage, and clustering of the viroids based on coverage using UMAP and DBSCAN. Validation through inoculation experiments confirmed the effectiveness of the algorithm in predicting the severity of disease symptoms induced by viroids. As the algorithm only requires the genome sequence data, it may be applied to any viroid and plant combination. These findings underscore a correlation between viroid pathogenicity and the genome sequences of viroid isolates and host plants, potentially aiding in the prevention of viroid outbreaks and the breeding of viroid‐resistant crops. [ABSTRACT FROM AUTHOR]
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- 2024
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35. Imported Buruli ulcer—is there risk for travellers?
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Norman, Francesca F and Chen, Lin H
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BURULI ulcer , *ETIOLOGY of diseases , *NON-communicable diseases , *MEDICAL specialties & specialists , *TRAVELERS , *LATENT infection - Abstract
This article provides information on the risk of imported Buruli ulcer for travelers. Buruli ulcer is a chronic disease caused by a bacterium and is common in tropical and subtropical countries. The number of cases has been decreasing, but the COVID-19 pandemic has affected reporting. The mode of transmission is uncertain, but contact with wounds and aquatic environments may be involved. The article summarizes reported cases of travel-related Buruli ulcer, including patient characteristics, treatment, and outcomes. Most cases were acquired in sub-Saharan Africa, and diagnosing the disease in non-endemic areas was challenging. The article also includes a table with information on reported cases from 1990 to 2023, including treatment and outcomes. The study highlights the diverse distribution and age range of Buruli ulcer cases, with most occurring in sub-Saharan Africa and Australia. Diagnosis can be difficult, and delays can lead to complications. It is important to consider Buruli ulcer in the diagnosis of non-healing ulcers in long-term travelers and migrants. [Extracted from the article]
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- 2024
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36. Infectious Diseases and Clinical Xenotransplantation.
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Fishman, Jay A. and Mueller, Nicolas J.
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XENOTRANSPLANTATION , *COMMUNICABLE diseases , *ACTINOBACILLUS pleuropneumoniae , *EMERGING infectious diseases , *CIRCOVIRUS diseases , *LABORATORY swine , *MEDICAL personnel , *LATENT infection , *MIDDLE East respiratory syndrome - Abstract
The article focuses on infectious diseases in the context of clinical xenotransplantation, exploring the implications and challenges posed by transferring animal organs into human recipients, with an emphasis on managing infectious risks and ensuring patient safety in this evolving field of medical practice.
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- 2024
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37. Evaluation of serial QuantiFERON‐TB Gold in tube test results and tuberculosis infection status in patients with psoriasis receiving anti‐IL‐17 treatment (secukinumab and ixekizumab): Real‐world data from a tuberculosis‐endemic country.
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Erbağcı, Ece, Koç Yıldırım, Sema, and Hapa, Fatma Aslı
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HIV seroconversion , *LATENT infection , *TUBERCULOSIS , *PSORIASIS , *INFECTION , *DISEASE duration - Abstract
Background Methods Results Conclusion In comparison with TNF‐α inhibitors, anti‐IL‐17A agents are considered to have a lower risk of active tuberculosis (TB) or latent TB infection (LTBI) reactivation.In this study, we aimed to evaluate the TB infection status and serial QuantiFERON‐TB‐Gold in tube test (QFT) results of psoriasis patients using IL‐17 inhibitors (secukinumab [SEC] and ixekizumab [IXE]) in a real‐world setting from a tuberculosis‐endemic country. Patients who used an anti‐IL‐17 agent for at least 3 months in our follow‐up were included in the study. Patients' clinical and demographic features, baseline QFT results and latest QFT results (if any), and TB infection status were noted from the past medical records.A total of 717 patients, of whom 333 (46.4%) were female, were included in the study. The cumulative exposure time to an anti‐IL‐17 agent was 14,147 patient‐months, 9743 patient‐months for SEC and 4404 patient‐months for IXE. Also, 459 (SEC = 305/IXE = 154) patients used an anti‐IL‐17 agent for ≥ 12 months. Of these, 125 had positive baseline QFT results. In all, 334 had negative baseline QFT results. The latest QFT result of 309 was also negative (persistent seronegative group). During follow‐up, the QFT results of 10 patients changed from negative to positive (positive seroconversion group). Seven of them were using SEC and three were using IXE, respectively. No case of active TB infection was detected.In our study, the positive seroconversion rate of 10/334 seems high, but this did not translate to active disease. However, closer monitoring may be required, especially in patients with advanced age, the presence of PsA, long disease duration and long anti‐IL‐17 treatment duration. [ABSTRACT FROM AUTHOR]
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- 2024
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38. Herpes Zoster Ophthalmicus: Presentation, Complications, Treatment, and Prevention.
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Litt, John, Cunningham, Anthony L., Arnalich-Montiel, Francisco, and Parikh, Raunak
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OPHTHALMIC zoster , *HERPES zoster , *CHICKENPOX , *MEDICAL personnel , *LATENT infection , *HERPES zoster vaccines , *VACCINE effectiveness - Abstract
Herpes zoster (HZ) is caused by reactivation of latent infection of varicella zoster virus (VZV) in sensory (cranial, dorsal root) ganglia. Major risk factors for HZ are increasing age and immunosuppression. HZ ophthalmicus (HZO) is a subset of HZ with involvement of the ophthalmic division of the fifth cranial trigeminal nerve. Approximately 4–20% of patients with HZ develop HZO. Approximately 50% of patients with HZO develop ocular disease, among whom up to 25% develop chronic or recurrent disease. Common manifestations of ocular disease include conjunctivitis, keratitis, and uveitis, whereas optic neuropathy and retinitis are uncommon. Due to the potential for vision impairment, ocular involvement requires urgent ophthalmic consultation. Early recognition and timely treatment with antivirals may prevent ocular complications. HZO is preventable by vaccination against HZ. Vaccine efficacy/effectiveness studies have been largely conducted for HZ with few studies assessing HZO. Both the recombinant adjuvanted vaccine (RZV) and live-attenuated vaccine (ZVL) significantly reduce the incidence of HZ and HZO in older adults. RZV is more effective than ZVL. Data on the effectiveness of vaccines for prevention of recurrent disease in patients with HZO are limited; however, vaccination is recommended. Despite recommendations to vaccinate individuals likely to benefit from an HZ vaccine, coverage for adults remains suboptimal. Barriers to vaccination include patient beliefs about HZ or HZ vaccines, and factors related to healthcare providers. In particular, the lack of a recommendation from their primary care physician is often cited by patients as a reason for remaining unvaccinated. By encouraging vaccination against HZ, physicians not only prevent HZ and HZO but also potential vision loss due to HZO. Graphical abstract available for this article. Plain Language Summary: Shingles, also known as herpes zoster, is a common and painful rash that develops when the virus that causes chickenpox in children reactivates, most often in adults. When shingles affects the eye or the area surrounding the eye, it is called herpes zoster ophthalmicus, or HZO for short. Up to one-fifth of people with shingles have HZO, and this risk increases with age and in people with other conditions that affect their immune system. Common signs and symptoms include a rash on the face, pain, fever, and headache, as well as symptoms in the eye, such as discomfort, redness, and discharge. HZO has the potential to cause permanent vision loss, and because of this, it is important that people with symptoms are referred to an eye doctor ("ophthalmologist") as soon as possible. Early diagnosis of HZO is essential for effective treatment and prevention of the more serious complications it can cause. Treatment within 3 days of the symptoms occurring, with medications known as antivirals, can shorten the duration of a shingles episode and help relieve the pain. To help prevent the risk of shingles and its subtypes like HZO, vaccination is recommended. Two vaccines are currently approved for the prevention of shingles in adults. Although these vaccinations are recommended, some people do not have them for various reasons, which include their own personal beliefs about vaccinations or that their doctor has not recommended it to them. It is important that vaccinations against shingles are recommended to all patients eligible to receive one. [ABSTRACT FROM AUTHOR]
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- 2024
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39. tRF‐Glu‐TTC‐026 as novel diagnostic biomarkers for active tuberculosis and regulates intracellular survival of Mycobacterium tuberculosis in macrophages by regulating macrophage polarization.
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Huang, Zikun, Xiong, Cuifen, Luo, Qing, Zhu, Juxiang, Guo, Yongqin, Fu, Peng, Zhu, Haiyan, Xu, Jianqing, Guo, Yang, Peng, Yiping, Qing, Cheng, Li, Junming, and Le, Aiping
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MONONUCLEAR leukocytes , *LATENT infection , *TUMOR necrosis factors , *MYCOBACTERIUM tuberculosis , *RECEIVER operating characteristic curves - Abstract
A study published in Clinical & Translational Medicine explores the potential of transfer RNA-derived small RNAs (tsRNAs) as diagnostic biomarkers for active tuberculosis (TB). The study identified 128 tsRNAs with differing expression patterns in peripheral blood mononuclear cells (PBMCs) of TB patients. Among these, tRF-Glu-TTC-026 showed promise as a diagnostic marker, with high sensitivity and specificity in distinguishing TB patients from non-TB individuals. Additionally, the study found that tRF-Glu-TTC-026 promotes the intracellular survival of Mycobacterium tuberculosis in macrophages by regulating macrophage polarization. Further research is needed to understand the mechanism and potential treatment strategies based on tsRNAs for TB control. [Extracted from the article]
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- 2024
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40. Neuronal expression of herpes simplex virus-1 VP16 protein induces pseudorabies virus escape from silencing and reactivation.
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Hsu, Zhi-Shan, Engel, Esteban A., Enquist, Lynn W., and Koyuncu, Orkide O.
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HUMAN herpesvirus 1 , *GENE expression , *AUJESZKY'S disease virus , *CUCUMBER mosaic virus , *PERIPHERAL nervous system , *LATENT infection - Abstract
Alpha herpesvirus (α-HV) particles enter their hosts from mucosal surfaces and efficiently maintain fast transport in peripheral nervous system (PNS) axons to establish infections in the peripheral ganglia. The path from axons to distant neuronal nuclei is challenging to dissect due to the difficulty of monitoring early events in a dispersed neuron culture model. We have established well-controlled, reproducible, and reactivateable latent infections in compartmented rodent neurons by infecting physically isolated axons with a small number of viral particles. This system not only recapitulates the physiological infection route but also facilitates independent treatment of isolated cell bodies or axons. Consequently, this system enables study not only of the stimuli that promote reactivation but also the factors that regulate the initial switch from productive to latent infection. Adeno-associated virus (AAV)-mediated expression of herpes simplex-1 (HSV-1) VP16 alone in neuronal cell bodies enabled the escape from silencing of incoming pseudorabies virus (PRV) genomes. Furthermore, the expression of HSV VP16 alone reactivated a latent PRV infection in this system. Surprisingly, the expression of PRV VP16 protein supported neither PRV escape from silencing nor reactivation. We compared transcription transactivation activity of both VP16 proteins in primary neurons by RNA sequencing and found that these homolog viral proteins produce different gene expression profiles. AAV-transduced HSV VP16 specifically induced the expression of proto-oncogenes including c-Jun and Pim2. In addition, HSV VP16 induces phosphorylation of c-Jun in neurons, and when this activity is inhibited, escape of PRV silencing is dramatically reduced. IMPORTANCE During latency, alpha herpesvirus genomes are silenced yet retain the capacity to reactivate. Currently, host and viral protein interactions that determine the establishment of latency, induce escape from genome silencing or reactivation are not completely understood. By using a compartmented neuronal culture model of latency, we investigated the effect of the viral transcriptional activator, VP16 on pseudorabies virus (PRV) escape from genome silencing. This model recapitulates the physiological infection route and enables the study of the stimuli that regulate the initial switch from a latent to productive infection. We investigated the neuronal transcriptional activation profiles of two homolog VP16 proteins (encoded by HSV-1 or PRV) and found distinct gene activation signatures leading to diverse infection outcomes. This study contributes to understanding of how alpha herpesvirus proteins modulate neuronal gene expression leading to the initiation of a productive or a latent infection. [ABSTRACT FROM AUTHOR]
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- 2024
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41. Regulatory role of Mycobacterium tuberculosis MtrA on dormancy/resuscitation revealed by a novel target gene-mining strategy.
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Xiang Fu, Xiaoyu Wan, Memon, Aadil Ahmed, Xiao-Yong Fan, Qiuhong Sun, Haifeng Chen, Yufeng Yao, Zixin Deng, Jian Ma, and Wei Ma
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MYCOBACTERIUM tuberculosis ,LATENT infection ,RESUSCITATION ,REGULATOR genes ,BINDING sites ,DORMANCY in plants - Abstract
Introduction: The unique dormancy of Mycobacterium tuberculosis plays a significant role in the major clinical treatment challenge of tuberculosis, such as its long treatment cycle, antibiotic resistance, immune escape, and high latent infection rate. Methods: To determine the function of MtrA, the only essential response regulator, one strategy was developed to establish its regulatory network according to high-quality genome-wide binding sites. Results and discussion: The complex modulation mechanisms were implied by the strong bias distribution of MtrA binding sites in the noncoding regions, and 32.7% of the binding sites were located inside the target genes. The functions of 288 potential MtrA target genes predicted according to 294 confirmed binding sites were highly diverse, and DNA replication and damage repair, lipid metabolism, cell wall component biosynthesis, cell wall assembly, and cell division were the predominant pathways. Among the 53 pathways shared between dormancy/resuscitation and persistence, which accounted for 81.5% and 93.0% of the total number of pathways, respectively, MtrA regulatory genes were identified not only in 73.6% of their mutual pathways, but also in 75.4% of the pathways related to dormancy/resuscitation and persistence respectively. These results suggested the pivotal roles of MtrA in regulating dormancy/resuscitation and the apparent relationship between dormancy/resuscitation and persistence. Furthermore, the finding that 32.6% of the MtrA regulons were essential in vivo and/or in vitro for M. tuberculosis provided new insight into its indispensability. The findings mentioned above indicated that MtrA is a novel promising therapeutic target for tuberculosis treatment since the crucial function of MtrA may be a point of weakness for M. tuberculosis. [ABSTRACT FROM AUTHOR]
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- 2024
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42. Herpes Zoster and Post-Herpetic Neuralgia—Diagnosis, Treatment, and Vaccination Strategies.
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Lim, Delwyn Zhi Jie, Tey, Hong Liang, Salada, Brenda Mae Alferez, Oon, Jolene Ee Ling, Seah, Ee-Jin Darren, Chandran, Nisha Suyien, and Pan, Jiun Yit
- Subjects
OPHTHALMIC zoster ,HERPES zoster ,HERPES zoster vaccines ,LATENT infection ,VARICELLA-zoster virus - Abstract
Introduction: Herpes zoster is caused by the reactivation of latent varicella infection within the sensory ganglia, caused by the varicella-zoster virus (VZV). The disease is classically characterized by a painful unilateral vesicular eruption. Complications of the disease include herpes zoster ophthalmicus, Ramsay Hunt syndrome, acute retinal necrosis, and post-herpetic neuralgia. In this paper, we discuss the epidemiology, pathogenesis, clinical features, diagnosis, management, and vaccination strategies of herpes zoster and post-herpetic neuralgia. Method: This paper was developed with input from specialists from Singapore's public sectors—dermatologists, family physicians, and infectious diseases specialists. Results: The diagnosis of herpes zoster is clinical and can be aided with laboratory investigations. Early initiation of antivirals, within 72 h of onset, can reduce the severity and duration of the condition and decrease the intensity of pain. In patients with a high risk of post-herpetic neuralgia, early initiation of anticonvulsants or tricyclic antidepressants can be considered. Herpes zoster is highly preventable, with the advent of the recombinant zoster vaccine (RZV) providing an overall vaccine efficacy of 97.2%. Procedures such as epidural blocks and subcutaneous or intracutaneous injections of local anesthetics and steroids can be considered for patients with a high risk of post-herpetic neuralgia to reduce its incidence. Conclusion: This article serves as a guideline for clinicians in the diagnosis, investigations, management, and prevention of herpes zoster. With the majority of adults in Singapore currently at risk of developing herpes zoster due to varicella immunization being only introduced in 2020, it is important for clinicians to recognize and manage herpes zoster appropriately. [ABSTRACT FROM AUTHOR]
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- 2024
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43. Exosomal Small RNA Sequencing Profiles in Plasma from Subjects with Latent Mycobacterium tuberculosis Infection.
- Author
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Cui, Xiaogang, Meng, Hangting, Li, Miao, Chen, Xia, Yuan, Dan, and Wu, Changxin
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LATENT tuberculosis ,NON-coding RNA ,GENE expression ,LATENT infection ,MYCOBACTERIUM tuberculosis - Abstract
Despite huge efforts, tuberculosis (TB) is still a major public health threat worldwide, with approximately 23% of the human population harboring a latent TB infection (LTBI). LTBI can reactivate and progress to active and transmissible TB disease, contributing to its spread within the population. The challenges in diagnosing and treating LTBI patients have been major factors contributing to this phenomenon. Exosomes offer a novel avenue for investigating the process of TB infection. In this study, we conducted small RNA sequencing to investigate the small RNA profiles of plasma exosomes derived from individuals with LTBI and healthy controls. Our findings revealed distinct miRNA profiles in the exosomes between the two groups. We identified 12 differentially expressed miRNAs through this analysis, which were further validated via qRT-PCR using the same exosomes. Notably, six miRNAs (hsa-miR-7850-5p, hsa-miR-1306-5p, hsa-miR-363-5p, hsa-miR-374a-5p, hsa-miR-4654, has-miR-6529-5p, and hsa-miR-140-5p) exhibited specifically elevated expression in individuals with LTBI. Gene ontology and KEGG pathway analyses revealed that the targets of these miRNAs were enriched in functions associated with ferroptosis and fatty acid metabolism, underscoring the critical role of these miRNAs in regulating the intracellular survival of Mycobacterium tuberculosis (Mtb). Furthermore, our results indicated that the overexpression of miR-7850-5p downregulated the expression of the SLC11A1 protein in both Mtb-infected and Mtb-uninfected THP1 cells. Additionally, we observed that miR-7850-5p promoted the intracellular survival of Mtb by suppressing the expression of the SLC11A1 protein. Overall, our findings provide valuable insights into the role of miRNAs and repetitive region-derived small RNAs in exosomes during the infectious process of Mtb and contribute to the identification of potential molecular targets for the detection and diagnosis of latent tuberculosis. [ABSTRACT FROM AUTHOR]
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- 2024
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44. Tissue and cellular tropism of Eptesicus fuscus gammaherpesvirus in big brown bats, potential role of pulmonary intravascular macrophages.
- Author
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Perdrizet, Ursula G., Hill, Janet E., Sobchishin, LaRhonda, Singh, Baljit, Fernando, Champika, Bollinger, Trent K., and Misra, Vikram
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VIRAL tropism ,CAPILLARIES ,ANTIGEN presenting cells ,LYMPHOID tissue ,WHOLE genome sequencing ,LATENT infection ,BATS - Abstract
Gammaherpesviruses (γHVs) are recognized as important pathogens in humans but their relationship with other animal hosts, especially wildlife species, is less well characterized. Our objectives were to examine natural Eptesicus fuscus gammaherpesvirus (EfHV) infections in their host, the big brown bat (Eptesicus fuscus), and determine whether infection is associated with disease. In tissue samples from 132 individual big brown bats, EfHV DNA was detected by polymerase chain reaction in 41 bats. Tissues from 59 of these cases, including 17 from bats with detectable EfHV genomes, were analyzed. An EfHV isolate was obtained from one of the cases, and electron micrographs and whole genome sequencing were used to confirm that this was a unique isolate of EfHV. Although several bats exhibited various lesions, we did not establish EfHV infection as a cause. Latent infection, defined as RNAScope probe binding to viral latency-associated nuclear antigen in the absence of viral envelope glycoprotein probe binding, was found within cells of the lymphoid tissues. These cells also had colocalization of the B-cell probe targeting CD20 mRNA. Probe binding for both latency-associated nuclear antigen and a viral glycoprotein was observed in individual cells dispersed throughout the alveolar capillaries of the lung, which had characteristics of pulmonary intravascular macrophages. Cells with a similar distribution in bat lungs expressed major histocompatibility class II, a marker for antigen presenting cells, and the existence of pulmonary intravascular macrophages in bats was confirmed with transmission electron microscopy. The importance of this cell type in γHVs infections warrants further investigation. [ABSTRACT FROM AUTHOR]
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- 2024
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45. Origins of the problematic E in SEIR epidemic models
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Donald S. Burke
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SEIR model ,Exposed ,Latent infection ,History ,Notation ,Infectious and parasitic diseases ,RC109-216 - Abstract
During the COVID-19 pandemic, over one thousand papers were published on “Susceptible-Exposed-Infectious-Removed” (SEIR) epidemic computational models. The English word “exposed” in its vernacular and public health usage means a state of having been in contact with an infectious individual, but not necessarily infected. In contrast, the term “exposed” in SEIR modeling usage typically stands for a state of already being infected but not yet being infectious to others, a state more properly termed “latently infected.” In public health language, “exposed” means possibly infected, yet in SEIR modeling language, “exposed” means already infected. This paper retraces the conceptual and mathematical origins of this terminological disconnect and concludes that epidemic modelers should consider using the “SLIR” notational short-hand (L for Latent) instead of SEIR.
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- 2024
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46. Comprehensive meta-analysis of severe fever with thrombocytopenia syndrome virus infections in humans, vertebrate hosts and questing ticks.
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Xu, Ao-Long, Xue, Han, Li, Yi, Wang, Xu, Zheng, Jin-Xin, Shi, Fu-Yan, Cui, Qing-Xia, Lu, Yan, Cun, De-Jiao, and Li, Lan-Hua
- Subjects
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TICKS , *VIRUS diseases , *RANDOM effects model , *LATENT infection , *VERTEBRATES , *THROMBOCYTOPENIA , *TICK infestations - Abstract
Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonosis caused by the SFTS virus (SFTSV). Understanding the prevalence of SFTSV RNA in humans, vertebrate hosts and ticks is crucial for SFTS control. Methods: A systematic review and meta-analysis were conducted to determine the prevalence of SFTSV RNA in humans, vertebrate hosts and questing ticks. Nine electronic databases were searched for relevant publications, and data on SFTSV RNA prevalence were extracted. Pooled prevalence was estimated using a random effects model. Subgroup analysis and multivariable meta-regression were performed to investigate sources of heterogeneity. Results: The pooled prevalence of SFTSV RNA in humans was 5.59% (95% confidence interval [CI] 2.78–9.15%) in those in close contact (close contacts) with infected individuals (infected cases) and 0.05% (95% CI 0.00–0.65%) in healthy individuals in endemic areas. The SFTSV infection rates in artiodactyls (5.60%; 95% CI 2.95–8.96%) and carnivores (6.34%; 95% CI 3.27–10.23%) were higher than those in rodents (0.45%; 95% CI 0.00–1.50%). Other animals, such as rabbits, hedgehogs and birds, also played significant roles in SFTSV transmission. The genus Haemaphysalis was the primary transmission vector, with members of Ixodes, Dermacentor, and Amblyomma also identified as potential vectors. The highest pooled prevalence was observed in adult ticks (1.03%; 95% CI 0.35–1.96%), followed by nymphs (0.66%; 95% CI 0.11–1.50%) and larvae (0.01%; 95% CI 0.00–0.46%). The pooled prevalence in ticks collected from endemic areas (1.86%; 95% CI 0.86–3.14%) was higher than that in ticks collected in other regions (0.41%; 95% CI 0.12–0.81%). Conclusions: Latent SFTSV infections are present in healthy individuals residing in endemic areas, and close contacts with SFTS cases are at a significantly higher risk of infection. The type of animal is linked to infection rates in vertebrate hosts, while infection rates in ticks are associated with the developmental stage. Further research is needed to investigate the impact of various environmental factors on SFTSV prevalence in vertebrate hosts and ticks. [ABSTRACT FROM AUTHOR]
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- 2024
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47. Autophagy-related molecular clusters identified as indicators for distinguishing active and latent TB infection in pediatric patients.
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Yu, Yang, Hua, Jie, and Chen, Liang
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MOLECULAR clusters ,CONTACT tracing ,LATENT infection ,AUTOPHAGY ,CHILD patients ,LATENT tuberculosis ,STANDARD deviations - Abstract
Background: Autophagy is crucial for controlling the manifestation of tuberculosis. This study intends to discover autophagy-related molecular clusters as biomarkers for discriminating between latent tuberculosis (LTBI) and active tuberculosis (ATB) in children through gene expression profile analysis. Methods: The expression of autophagy modulators was examined in pediatric patients with LTBI and ATB utilizing public datasets from the Gene Expression Omnibus (GEO) collection (GSE39939 and GSE39940). Results: In a training dataset (GSE39939), patients with LTBI and ATB exhibited the expression of autophagy-related genes connected with their active immune responses. Two molecular clusters associated with autophagy were identified. Compared to Cluster 1, Cluster 2 was distinguished through decreased adaptive cellular immune response and enhanced inflammatory activation, according to single-sample gene set enrichment analysis (ssGSEA). Per the study of gene set variation, Cluster 2's differentially expressed genes (DEGs) played a role in synthesizing transfer RNA, DNA repair and recombination, and primary immunodeficiency. The peak variation efficiency, root mean square error, and area under the curve (AUC) (AUC = 0.950) were all lowered in random forest models. Finally, a seven-gene-dependent random forest profile was created utilizing the CD247, MAN1C1, FAM84B, HSZFP36, SLC16A10, DTX3, and SIRT4 genes, which performed well against the validation dataset GSE139940 (AUC = 0.888). The nomogram calibration and decision curves performed well in identifying ATB from LTBI. Conclusions: In summary, according to the present investigation, autophagy and the immunopathology of TB might be correlated. Furthermore, this investigation established a compelling prediction expression profile for measuring autophagy subtype development risks, which might be employed as possible biomarkers in children to differentiate ATB from LTBI. [ABSTRACT FROM AUTHOR]
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- 2024
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48. Framework for implementing collaborative TB-silicosis activities in India: insights from an expert panel.
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Rupani, Mihir P., Nimavat, Pankaj, Patel, Yogesh, Shah, Harsh D., and Sau, Arkaprabha
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SILICOSIS ,SILICA dust ,LATENT infection ,OCCUPATIONAL diseases ,OCCUPATIONAL exposure ,DIAGNOSIS - Abstract
Tuberculosis (TB) treatment is more challenging for patients with silicosis, as it complicates the diagnosis of both diseases and increases mortality risk. Silicosis, an incurable occupational disease, confounds the diagnosis of TB and vice versa, making it more difficult to accurately identify and treat either condition. Moreover, TB appears to accelerate the progression of silicosis. Exposure to silica dust, a common cause of silicosis, can also trigger latent TB to become active TB. This correspondence outlines a proposed framework for implementing collaborative TB-silicosis activities in India, aimed at improving early diagnosis and management for both diseases. An expert panel of medical professionals developed this framework through online consultations in October and November 2022. The panel's goal was to establish a consensus on integrating TB-silicosis activities, with a focus on early detection and proper management. The framework suggests testing all patients with silicosis for active TB and screening workers exposed to silica dust for latent TB infection. It also recommends that patients with TB who have a history of occupational exposure to silica dust should be tested for silicosis. Reliable diagnostic tools, such as chest X-rays, are emphasized, providing guidance on their use for both diseases. The proposed collaborative TB-silicosis framework offers a structured approach to identifying and managing these two diseases, contributing to the global goal of eliminating silicosis by 2030 and aligning with the World Health Organization's targets for reducing TB incidence and mortality. It recommends specific strategies for implementation, including testing, referral systems, and workplace-based interventions. The framework also underscores the need for coordinated efforts among stakeholders, including the ministries of health, labor, industry, and environment. This correspondence provides valuable insights into how India can successfully implement collaborative TB-silicosis activities, serving as a model for other regions with similar challenges. [ABSTRACT FROM AUTHOR]
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- 2024
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49. Mixed methods study on latent tuberculosis among agate stone workers and advocacy for testing silica dust exposed individuals in India.
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Rupani, Mihir P., Balachandar, Rakesh, Kharkwal, Gitika, Kulkarni, Nikhil P., Modi, Bhavesh V., Asodia, Rutu N., Vaghela, Krishna K., and Nimavat, Deizy R.
- Subjects
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LATENT tuberculosis , *SILICA dust , *DUST , *LATENT infection , *BCG vaccines , *INDUSTRIAL hygiene - Abstract
The 2021 tuberculosis (TB) preventive treatment guidelines in India included silicosis as a screening group, yet latent TB infection (LTBI) testing for silica-dust-exposed individuals is underemphasized. Focusing on an estimated 52 million silica-dust-exposed workers, particularly agate-stone workers in Khambhat, Gujarat, our study aims to estimate LTBI prevalence, identify predictors, and gather insights from TB and silicosis experts. Employing a sequential explanatory mixed-methods approach, a cross-sectional study involved 463 agate-stone workers aged ≥ 20 years in Khambhat, using IGRA kits for LTBI testing. In-depth interviews with experts complemented quantitative findings. Among agate-stone workers, 58% tested positive for LTBI, with predictors including longer exposure, type of work, and BCG vaccination. Our findings reveal a nearly double burden of LTBI compared to the general population, particularly in occupations with higher silica dust exposure. Experts advocate for including silica-dust-exposed individuals in high-risk groups for LTBI testing, exploring cost-effective alternatives like improved skin sensitivity tests, and shorter TB preventive treatment regimens to enhance compliance. Future research should explore upfront TB preventive treatment for silica-dust-exposed individuals with high LTBI prevalence and optimal exposure duration. This study underscores the urgent need for policy changes and innovative approaches to TB prevention among silica-dust-exposed populations, impacting global occupational health strategies. [ABSTRACT FROM AUTHOR]
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- 2024
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50. Individualized lipid profile in urine-derived extracellular vesicles from clinical patients with Mycobacterium tuberculosis infections.
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Lingna Lyu, Hongyan Jia, Qiuyue Liu, Wenxia Ma, Zihui Li, Liping Pan, and Xiuli Zhang
- Subjects
MYCOBACTERIUM tuberculosis ,MYCOBACTERIAL diseases ,EXTRACELLULAR vesicles ,LATENT tuberculosis ,LATENT infection ,LIPOLYSIS ,LIPIDS - Abstract
Background: Lipids are a key nutrient source for the growth and reproduction of Mycobacterium tuberculosis (Mtb). Urine-derived extracellular vesicles (EVs), because of its non-invasive sampling, lipid enrichment, and specific sorting character, have been recognized as a promising research target for biomarker discovery and pathogenesis elucidation in tuberculosis (TB). We aim to profile lipidome of Mtb-infected individuals, offer novel lipid signatures for the development of urine-based TB testing, and provide new insights into the lipid metabolism after Mtb infection. Methods: Urine-derived extracellular vesicles from 41 participants (including healthy, pulmonary tuberculosis, latent tuberculosis patients, and other lung disease groups) were isolated and individually detected using targeted lipidomics and proteomics technology platforms. Biomarkers were screened by multivariate and univariate statistical analysis and evaluated by SPSS software. Correlation analyses were performed on lipids and proteins using the R Hmisc package. Results: Overall, we identified 226 lipids belonging to 14 classes. Of these, 7 potential lipid biomarkers for TB and 6 for latent TB infection (LTBI) were identified, all of which were classified into diacylglycerol (DAG), monoacylglycerol (MAG), free fatty acid (FFA), and cholesteryl ester (CE). Among them, FFA (20:1) was the most promising biomarker target in diagnosing TB/LTBI from other compared groups and also have great diagnostic performance in distinguishing TB from LTBI with AUC of 0.952. In addition, enhanced lipolysis happened as early as individuals got latent Mtb infection, and ratio of raft lipids was gradually elevated along TB progression. Conclusion: This study demonstrated individualized lipid profile of urinary EVs in patients with Mtb infection, revealed novel potential lipid biomarkers for TB/LTBI diagnosis, and explored mechanisms by which EV lipid raft-dependent bio-processes might affect pathogenesis. It lays a solid foundation for the subsequent diagnosis and therapeutic intervention of TB. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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