Volume 15, Issue 1, December 2024 .

Proceedings of the National Academy of Sciences, Volume 121, Issue 37, September 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 37, September 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 37, September 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 37, September 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 37, September 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 37, September 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 37, September 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 37, September 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 37, September 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 37, September 2024.

Proceedings of the National Academy of Sciences, Volume 121, Issue 37, September 2024.

Abstract Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes widespread changes in epigenetic modifications and chromatin architecture in the host cell. Recent evidence suggests that SARS-CoV-2 non-structural protein 1 (nsp1) plays an important role in driving these changes. Previously thought to be primarily involved in host translation shutoff and cellular mRNA degradation, nsp1 has now been shown to be a truly multifunctional protein that affects host gene expression at multiple levels. The functions of nsp1 are surprisingly diverse and include not only the downregulation of cellular mRNA translation and stability, but also the inhibition of mRNA export from the nucleus, the suppression of host immune signaling, and, most recently, the epigenetic regulation of host gene expression. In this review, we first summarize the current knowledge on SARS-CoV-2-induced changes in epigenetic modifications and chromatin structure. We then focus on the role of nsp1 in epigenetic reprogramming, with a particular emphasis on the silencing of immune-related genes. Finally, we discuss potential molecular mechanisms underlying the epigenetic functions of nsp1 based on evidence from SARS-CoV-2 interactome studies.

Volume 13, Issue 1, December 2024 .

Volume 13, Issue 1, December 2024 .

Volume 13, Issue 1, December 2024 .

by Wei-Li Hsu, Chung-Lun Chen, Shi-Wei Huang, Chia-Chen Wu, I-Hsuan Chen, Muthukumar Nadar, Yin-Peng Su, Ching-Hsiu Tsai …

by Abdualrahman Saeed Alshehry This study assessed the resilience of nurses in Saudi Arabia during the corona virus 2019 (COVID-19) pandemic and examined its influence on their quality of life (QOL). A sample of 356 nurses was surveyed in this quantitative, cross-sectional study using the Resilience Scale for Nurses and the World Health Organization Quality of Life (WHOQOL-BREF) from October 2020 to March 2021. The nurses reported the highest resilience score on “situational pattern”, while the lowest score was on “relational pattern.” The nurses had good perceptions on their overall QOL and health and rated their “social relationship” as having the highest quality, while their “environmental” domain as having the least quality. Gender, marital status, provision of direct nursing care to COVID-19 patients, “philosophical pattern”, “situational pattern” and “dispositional pattern” had multivariate impacts on the QOL dimensions. The study concluded that being resilient can positively impact the nurses’ QOL during stressful situations, such as the COVID-19 pandemic.

by Julia Smith, Muhammad Haaris Tiwana, Alice Murage, Hasina Samji, Rosemary Morgan, Jorge Andres Delgado-Ron While there is growing literature on experiences of healthcare workers and those providing unpaid care during COVID-19, little research considers the relationships between paid and unpaid care burdens and contributions. We administered a moral distress survey to healthcare workers in Canada, in 2022, collecting data on both paid and unpaid care. There were no significant differences in the proportion of participants providing unpaid care by gender, with both genders equally affected by certain responsibilities such as reduced contact with family/loved ones. However, men were significantly more distressed about specific unpaid care responsibilities. Unpaid care was not significantly associated with differences in intention to leave work. At work, women were significantly more concerned about patients unable to see family, while men were distressed by others mistreating COVID patients. This study enhances understanding of paid and unpaid care relationships, particularly during crises, and proposes an innovative method for assessing unpaid care burdens.

by Sonoko Matsumoto, Takashi Shimizu, Akihiko Uda, Kenta Watanabe, Masahisa Watarai Francisella tularensis is a causative agent of the zoonotic disease tularemia, and is highly pathogenic to humans. The pathogenicity of this bacterium is largely attributed to intracellular growth in host cells. Although several bacterial factors important for the intracellular growth have been elucidated, including the type VI secretion system, the host factors involved in the intracellular growth of F. tularensis are largely unknown. To identify the host factors important for F. tularensis infection, 368 compounds were screened for the negative regulation of F. tularensis subsp. novicida (F. novicida) infection. Consequently, 56 inhibitors were isolated that decreased F. novicida infection. Among those inhibitors, we focused on cucurbitacin I, an inhibitor of the JAK2/ STAT3 pathway. Cucurbitacin I and another JAK2/STAT3 inhibitor, Stattic, decreased the intracellular bacterial number of F. novicida. However, these inhibitors failed to affect the cell attachment or the intrasaccular proliferation of F. novicida. In addition, treatment with these inhibitors destabilized actin filaments. These results suggest that the JAK2/STAT3 pathway plays an important role in internalization of F. novicida into host cells through mechanisms involving actin dynamics, such as phagocytosis.

by Simone Leo, Michael R. Crusoe, Laura Rodríguez-Navas, Raül Sirvent, Alexander Kanitz, Paul De Geest, Rudolf Wittner, Luca Pireddu, Daniel Garijo, José M. Fernández, Iacopo Colonnelli, Matej Gallo, Tazro Ohta, Hirotaka Suetake, Salvador Capella-Gutierrez, Renske de Wit, Bruno P. Kinoshita, Stian Soiland-Reyes Recording the provenance of scientific computation results is key to the support of traceability, reproducibility and quality assessment of data products. Several data models have been explored to address this need, providing representations of workflow plans and their executions as well as means of packaging the resulting information for archiving and sharing. However, existing approaches tend to lack interoperable adoption across workflow management systems. In this work we present Workflow Run RO-Crate, an extension of RO-Crate (Research Object Crate) and Schema.org to capture the provenance of the execution of computational workflows at different levels of granularity and bundle together all their associated objects (inputs, outputs, code, etc.). The model is supported by a diverse, open community that runs regular meetings, discussing development, maintenance and adoption aspects. Workflow Run RO-Crate is already implemented by several workflow management systems, allowing interoperable comparisons between workflow runs from heterogeneous systems. We describe the model, its alignment to standards such as W3C PROV, and its implementation in six workflow systems. Finally, we illustrate the application of Workflow Run RO-Crate in two use cases of machine learning in the digital image analysis domain.

Infection and Immunity, Ahead of Print.

Infection and Immunity, Ahead of Print.

Abstract Purpose A host-protein signature score, consisting of serum-concentrations of C-reactive protein, tumour necrosis factor-related apoptosis-inducing ligand, and interferon gamma-induced protein 10, was validated for distinguishing between bacterial and viral infections as an antimicrobial stewardship measure for routine clinical practice among adult patients in a German tertiary hospital. Methods This single-centre, explorative study prospectively assessed the host-protein signature score, comparing it with serum procalcitonin (PCT) in patients with blood stream infections (BSI) and evaluating its efficacy in patients with viral infections against the standard of care (SOC) to assess the need for antibiotics due to suspected bacterial super/coinfection. Manufacturer-specified threshold scores were used to differentiate viral ( 65) infections. Results Ninety-seven patients (BSI [n = 56]; viral infections [n = 41]) were included. The score (cut-off score > 65) tended to detect BSI with higher sensitivity than did PCT (cut-off > 0.5 ng/mL) (87.5% vs. 76.6%). Three patients (5.4%) with BSI had a score  65, indicating bacterial superinfections. Additionally, 11 patients (26.8%) had scores 

Abstract Introduction Despite national guidelines and use of intrapartum antibiotic prophylaxis (IAP), Streptococcus agalactiae (group B streptococci (GBS)) is still a leading cause of morbidity and mortality in newborns in Europe and the United States. The European DEVANI (Design of a Vaccine Against Neonatal Infections) program assessed the neonatal GBS infection burden in Europe, the clinical characteristics of colonized women and microbiological data of GBS strains in colonized women and their infants with early-onset disease (EOD). Methods Overall, 1083 pregnant women with a GBS-positive culture result from eight European countries were included in the study. Clinical obstetrical information was collected by a standardized questionnaire. GBS strains were characterized by serological and molecular methods. Results Among GBS carriers included in this study after testing positive for GBS by vaginal or recto-vaginal sampling, 13.4% had at least one additional obstetrical risk factor for EOD. The five most common capsular types (i.e., Ia, Ib, II, III and V) comprised ~ 93% of GBS carried. Of the colonized women, 77.8% received any IAP, and in 49.5% the IAP was considered appropriate. In our cohort, nine neonates presented with GBS early-onset disease (EOD) with significant regional heterogeneity. Conclusions Screening methods and IAP rates need to be harmonized across Europe in order to reduce the rates of EOD. The epidemiological data from eight different European countries provides important information for the development of a successful GBS vaccine. …

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Journal of Medical Virology, Volume 96, Issue 9, September 2024.

Journal of Medical Virology, Volume 96, Issue 9, September 2024.

Journal of Medical Virology, Volume 96, Issue 9, September 2024.

Abstract Amlexanox (ALX) is a small molecule drug for the treatment of inflammatory, autoimmune, metabolic and tumor diseases. At present, there are no studies on whether ALX has a therapeutic effect on inflammatory bowel disease (IBD). In this study, we used a mouse model of dextran sulfate sodium (DSS)-induced colitis to investigate the effect of ALX targeted inhibition of TBK1 on colitis. We found that the severity of colitis in mice was correlated with TBK1 expression. Notably, although ALX inhibited the activation of the TBK1-NF-κB/TBK1-IRF3 pro-inflammatory signaling pathway, it exacerbated colitis and reduced survival in mice. The results of drug safety experiments ruled out a relationship between this exacerbating effect and drug toxicity. In addition, ELISA results showed that ALX promoted the secretion of IL-1β and IFN-α, and inhibited the production of cytokines IL-6, TNF-α, IL-10, TGF-β and secretory IgA. Flow cytometry results further showed that ALX promoted T cell proliferation, activation and differentiation, and thus played a pro-inflammatory role; Also, ALX inhibited the generation of dendritic cells and the polarization of macrophages to M1 type, thus exerting anti-inflammatory effect. These data suggest that the regulation of ALX on the function of different immune cells is different, so the effect on the inflammatory response is bidirectional. In conclusion, our study demonstrates that simply inhibiting TBK1 in all immune cells is not effective for the treatment of colitis. Further investigation the anti-inflammatory mechanism of ALX on dendritic cells and macrophages may provide a new strategy for the treatment of IBD.

Abstract The neurological complications of influenza affect mainly the pediatric Asian population. In the category of influenza-associated encephalopathy, acute necrotizing encephalopathy (ANE) is a rapidly progressive and fulminant brain disorder associated with significant neurological sequelae and mortality. To date, only a few adult cases of influenza-associated ANE have been reported. We describe a 44-year-old woman who presented with rapid progression of consciousness impairment and recurrent generalized convulsions. Influenza was diagnosed three days prior to presentation, and infection with influenza A (H3N2) pdm09 was subsequently confirmed. A diagnosis of ANE was made based on the presence of characteristic brain MRI findings, the exclusion of central nervous system infection, and an elevated serum interleukin-6 level. Pulse steroid therapy followed by tocilizumab was initiated, which led to clinical stabilization and improvement. Genetic testing revealed that the patient carried heterozygous human leukocyte antigen DQB1 03:03 and DRB1 09:01 genotypes. An analysis of the adult cases of influenza-associated ANE in the literature and the present case revealed a wide range of ages (22–71 years), a short interval (median 3 days) between the clinical onset of influenza and ANE, and a high overall mortality rate (32%). The thalamus was the most frequent (91%) location of the lesions. Our report highlights the importance of identifying this devastating but treatable neurological complication of influenza in adults, especially those of Asian descent. As a cytokine storm is the most accepted pathogenic mechanism for ANE, cytokine-directed therapies may be promising treatments for which further investigation is warranted. …

Abstract Background The Covid-19 pandemic has been characterized by the emergence of novel SARS-CoV-2 variants, each with distinct properties influencing transmission dynamics, immune escape, and virulence, which, in turn, influence their impact on local populations. Swift analysis of the properties of newly emerged variants is essential in the initial days and weeks to enhance readiness and facilitate the scaling of clinical and public health system responses. Methods This paper introduces a two-variant metapopulation compartmental model of disease transmission to simulate the dynamics of disease transmission during a period of transition to a newly dominant strain. Leveraging novel S-gene dropout analysis data and genomic sequencing data, combined with confirmed Covid-19 case data, we estimate the epidemiological characteristics of the Omicron variant, which replaced the Delta variant in late 2021 in Philadelphia, PA. We utilized a grid-search method to identify plausible combinations of model parameters, followed by an ensemble adjustment Kalman filter for parameter inference. Results The model successfully estimated key epidemiological parameters; we estimated the ascertainment rate of 0.22 (95% credible interval 0.15–0.29) and transmission rate of 5.0 (95% CI 2.4–6.6) for the Omicron variant. Conclusions The study demonstrates the potential for this model-inference framework to provide real-time insights during the emergence of novel variants, aiding in timely public health responses. …

Abstract Background The mortality risk of co-infections/secondary infections (CoI/ScI) is under-reported in patients with non-critical COVID-19, leading to the under-management of CoI/ScI and publication bias in the medical literature. We aimed to investigate the association between CoI/ScI and mortality in patients hospitalised with mild-to-severe COVID-19. Methods We conducted a retrospective cohort study at a COVID-19 treatment hospital in Vietnam and collected all eligible medical records, with CoI/ScI status as the exposure (non-CoI/ScI and CoI/ScI, with the latter including nature of pathogen [bacterial, fungal, or bacterial + fungal] and multidrug-resistance pathogen [no MDRp or ≥ 1 MDRp]). The outcome was all-cause mortality, defined as in-hospital death by all causes or being discharged under critical illness. We used time-dependent analysis to report rates of mortality with 95% confidence intervals (95% CI, Poisson regression) and hazard ratios (HR) with 95% CI (Cox proportional hazards regression with Holm’s method for multiplicity control). Results We followed 1466 patients (median age 61, 56.4% being female) for a median of 9 days. We recorded 387 (26.4%) deaths (95/144 [66.0%] in the CoI/ScI group and 292/1322 [22.1%] in the non-CoI/ScI group). Adjusted mortality rates (per 100 person-days) of the CoI/ScI (6.4, 95% CI 5.3 to 7.8), including bacterial (8.0, 95% CI 7.2 to 8.9), no MDRp (5.9, 95% CI 4.8 to 7.4), and ≥ 1 MDRp (9.0, 95% CI 8.2 to 10.0) groups were higher than that of the non-CoI/ScI group (2.0, 95% CI 1.8 to 2.2). These corresponded to higher risks of mortality in the overall CoI/ScI (HR 3.27, 95% CI 2.58 to 4.13, adjusted p 

Abstract Background Human adenovirus (HAdV) is an important pathogen causing acute respiratory infection (ARI) in children. Many countries, including China, have experienced sporadic or outbreaks related to HAdV-4, and death cases were reported. However, there is little research on HAdV-4 and the epidemic situation of HAdV-4 in China is little known. This study was designed to comprehend the prevalence and genetic characteristics of HAdV-4 in ARI children in China. Methods Respiratory tract samples from ARI children hospitalized in six hospitals of Northern and Southern China from 2017 to 2020 were collected for HAdV detection and typing. Clinical information was collected from HAdV-4 positive patients for clinical characteristics and epidemiological analysis. The main capsid proteins and the whole genome sequences were amplified and sequenced for bioinformatics analysis. Results There were 2847 ARI children enrolled, and 156 (5.48%) HAdV positive samples were detected. Eleven HAdV-4 positive samples were identified, accounting for 0.39% of the total samples and 7.05% of the HAdV positive samples. The main manifestations were fever and cough. Two children had conjunctivitis. Two children were diagnosed with severe pneumonia and developed respiratory failure. One of them developed hemophagocytic syndrome and checked in pediatric intensive care unit (PICU). This child had ventricular septal defect. All the children recovered. The isolated strains of HAdV-4 obtained in this study and the reference strains from China located in the same phylogenetic branch (HAdV-4a), while the prototype strain and vaccine strains formed another branch (HAdV-4p). Upon comparison with the prototype strain, there were a few amino acid mutations existing in three major capsid proteins. According to recombination analysis, no new recombination was found. Conclusions The detection rate of HAdV-4 in children hospitalized with ARI was 0.39% in the total samples and 7.05% of all HAdV positive samples. HAdV-4 isolates obtained in this study and other reference strains from China belonged to the HAdV-4a subtype. Our data provided reference for the monitoring, prevention and control of HAdV-4, as well as the research and development of vaccines and drugs. …

Abstract Background For decades, dengue has posed a significant threat as a viral infectious disease, affecting numerous human lives globally, particularly in tropical regions, yet no cure has been discovered. The genetic trait of vector competence in Aedes mosquitoes, which facilitates dengue transmission, is difficult to measure and highly sensitive to environmental changes. Methods In this study we attempt, for the first time in a non-laboratory setting, to quantify the vector competence of Aedes mosquitoes assuming its homogeneity across both species; aegypti and albopictus and across the four Dengue serotypes. Estimating vector competence in relation to varying rainfall patterns was focused in this study to showcase the changes in this vector trait with respect to environmental variables. We quantify it using an existing mathematical model originally developed for malaria in a Bayesian inferencing setup. We conducted this study in the Colombo district of Sri Lanka where the highest number of human populations are threatened with dengue. Colombo district experiences continuous favorable temperature and humidity levels throughout the year creating ideal conditions for Aedes mosquitoes to thrive and transmit the Dengue disease. Therefore we only used the highly variable and seasonal rainfall as the primary environmental variable as it significantly influences the number of breeding sites and thereby impacting the population dynamics of Aedes. Results Our research successfully deduced vector competence values for the four identified seasons based on Monsoon rainfalls experienced in Colombo within a year. We used dengue data from 2009 - 2022 to infer the estimates. These estimated values have been corroborated through experimental studies documented in the literature, thereby validating the malaria model to estimate vector competence for dengue disease. Conclusion Our research findings conclude that environmental conditions can amplify vector competence within specific seasons, categorized by their environmental attributes. Additionally, the deduced vector competence offers compelling evidence that it impacts disease transmission, irrespective of geographical location, climate, or environmental factors. …

Abstract Background While COVID-19 has been controlled and deaths have decreased, the long-term consequences of COVID-19 remain a challenge we face today. This study was conducted to determine the relationship between the apoptosis of lymphocyte cells with DNA damage and oxidative stress and the therapeutic and clinical outcomes of elderly patients with COVID-19. Methods This study was conducted from April 2020 to May 2021 (the period of severe attacks of the epidemic peak of COVID-19) and September 2022 (the post-COVID-19 period). The study groups included elderly patients with COVID-19 hospitalized in the ICU and normal wards of the hospital as well as elderly patients with influenza. A polymerase chain reaction was used to check the validity of the studied diseases. The Annexin V/Propidium Iodide method was used to evaluate the level of apoptosis. Genotoxic effects and DNA damage were assessed by the comet assay method. Total antioxidant status (TAS), total oxidant status (TOS), and myeloperoxidase activity (MPO) were measured by photometric methods. Results The highest level of apoptosis in peripheral blood lymphocytes and the highest level of DNA damage were observed at both times in the intubated-ICU and non-intubated-ICU groups. In all groups, there was a significant increase in peripheral blood lymphocyte apoptosis levels and DNA damage levels compared to the healthy control group (p 

Abstract Aims This study aims to evaluate the presence of EBV, HCMV, and BKV genomic sequences in the plasma samples (active infection/viremia) of kidney transplant recipients suspected of rejection and to investigate host and risk factors related to the activation of these viruses in these patients. Methods In this cross-sectional single-center study, plasma samples were collected from 98 suspected kidney transplant rejection patients at Labafinejad Hospital, Tehran, Iran, between December 2022 and June 2023. Quantitative real-time PCR assays for HCMV, EBV, and BK were performed using GeneProof Real-time PCR kits. ROC curve analysis was used to determine the viral load cutoff point for each virus. Findings HCMV active viremia was detected in 18 (18.36%) recipients, EBV active viremia in 7 (7.14%), and BKV active viremia in 5 (5.10%). ROC results indicated viral load cutoff points of 778, 661, and 457 points for HCMV, EBV, and BKV, respectively. The duration of time after transplantation significantly differed between active viremia and no viremia groups (120.5 vs. 46 months, P = 0.014). In the BKV active viremia group, the increase in creatinine compared to baseline creatinine was significantly higher than in the no viremia group (2.7 vs. 0.8, P = 0.017). The odds ratio of HCMV active viremia in patients taking tacrolimus was 2.84 times higher, and the odds of HCMV active viremia in patients taking antithymocyte globulin was 3.01 times higher than in patients not taking these drugs. Conclusion Rapid and timely diagnosis of viral active infections in kidney transplant patients is crucial for effective disease management and implementation of appropriate treatment strategies. Identifying potential risk factors, including host and treatment-related factors that influence transplantation, can facilitate the development of suitable preventive strategies. …

Abstract Background The use of antiretrovirals has increased the survival of People Living with HIV/AIDS (PLWHA), resulting in an aging population and a rise in the incidence of sarcopenia. The lack of uniformity among the prevalences found in studies may be associated with the use of different diagnostic criteria, highlighting the need for local studies to determine the prevalence of sarcopenia. Methods Cross-sectional study to estimate the prevalence and associated factors of sarcopenia using the revised criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). This study included PLWHA of both sexes, aged 40 years or older, who were treated at the infectious disease outpatient clinic of a tertiary hospital from 2019 to 2021. Muscle mass was quantified through electrical bioimpedance, using resistance and reactance to calculate appendicular lean mass (ALM) in kg/m². Muscle strength, measured in kg, was assessed using a manual dynamometer, and muscle function was evaluated using the gait speed test (m/s). Numerical variables were analyzed using measures of central tendency and dispersion. The chi-square test was used to assess associations in categorical variables. Odds ratios (OR) and 95% Confidence Intervals (CI) were calculated to evaluate the strength of associations. Results Among the 218 PLWHA, the prevalence of sarcopenia was 8.7% (95% CI: 5.6 to 13.3). The mean age of the study population was 51.8 ± 8.3 years; 53.7% were male, 72.9% were brown/Black, 97.7% reported not using illicit drugs, and 24.8% were classified as obese. Multivariate analysis showed that the time since HIV diagnosis (P = 0.022) and the use of illicit drugs were associated with the diagnosis of sarcopenia. Conclusion The prevalence of sarcopenia using the EWGSOP2 criteria was low. People with a longer duration of HIV infection and those using illicit drugs were more likely to develop sarcopenia. …

Abstract Background Coinfection with two phylogenetically distinct Human Immunodeficiency Virus-1 (HIV-1) variants might provide an opportunity for rapid viral expansion and the emergence of fit variants that drive disease progression. However, autologous neutralising immune responses are known to drive Envelope (Env) diversity which can either enhance replicative capacity, have no effect, or reduce viral fitness. This study investigated whether in vivo outgrowth of coinfecting variants was linked to pseudovirus and infectious molecular clones’ infectivity to determine whether diversification resulted in more fit virus with the potential to increase disease progression. Results For most participants, emergent recombinants displaced the co-transmitted variants and comprised the major population at 52 weeks postinfection with significantly higher entry efficiency than other co-circulating viruses. Our findings suggest that recombination within gp41 might have enhanced Env fusogenicity which contributed to the increase in pseudovirus entry efficiency. Finally, there was a significant correlation between pseudovirus entry efficiency and CD4 + T cell count, suggesting that the enhanced replicative capacity of recombinant variants could result in more virulent viruses. Conclusion Coinfection provides variants with the opportunity to undergo rapid recombination that results in more infectious virus. This highlights the importance of monitoring the replicative fitness of emergent viruses. …

Abstract Background Bacillus anthracis is a highly pathogenic bacterium that can cause lethal infection in animals and humans, making it a significant concern as a pathogen and biological agent. Consequently, accurate diagnosis of B. anthracis is critically important for public health. However, the identification of specific marker genes encoded in the B. anthracis chromosome is challenging due to the genetic similarity it shares with B. cereus and B. thuringiensis. Methods The complete genomes of B. anthracis, B. cereus, B. thuringiensis, and B. weihenstephanensis were de novo annotated with Prokka, and these annotations were used by Roary to produce the pan-genome. B. anthracis exclusive genes were identified by Perl script, and their specificity was examined by nucleotide BLAST search. A local BLAST alignment was performed to confirm the presence of the identified genes across various B. anthracis strains. Multiplex polymerase chain reactions (PCR) were established based on the identified genes. Result The distribution of genes among 151 whole-genome sequences exhibited three distinct major patterns, depending on the bacterial species and strains. Further comparative analysis between the three groups uncovered thirty chromosome-encoded genes exclusively present in B. anthracis strains. Of these, twenty were found in known lambda prophage regions, and ten were in previously undefined region of the chromosome. We established three distinct multiplex PCRs for the specific detection of B. anthracis by utilizing three of the identified genes, BA1698, BA5354, and BA5361. Conclusion The study identified thirty chromosome-encoded genes specific to B. anthracis, encompassing previously described genes in known lambda prophage regions and nine newly discovered genes from an undefined gene region to the best of our knowledge. Three multiplex PCR assays offer an accurate and reliable alternative method for detecting B. anthracis. Furthermore, these genetic markers have value in anthrax vaccine development, and understanding the pathogenicity of B. anthracis. …

Abstract Background HIV-1 has well-established mechanisms to disrupt essential pathways in people with HIV, such as inflammation and metabolism. Moreover, diversity of the amino acid sequences in fundamental HIV-1 proteins including Tat and Vif, have been linked to dysregulating these pathways, and subsequently influencing clinical outcomes in people with HIV. However, the relationship between Tat and Vif amino acid sequence variation and specific immune markers and metabolites of the tryptophan-kynurenine (Trp-Kyn) pathway remains unclear. Therefore, this study aimed to investigate the relationship between Tat/Vif amino acid sequence diversity and Trp-Kyn metabolites (quinolinic acid (QUIN), Trp, kynurenic acid (KA), Kyn and Trp/Kyn ratio), as well as specific immune markers (sCD163, suPAR, IL-6, NGAL and hsCRP) in n = 67 South African cART-naïve people with HIV. Methods Sanger sequencing was used to determine blood-derived Tat/Vif amino acid sequence diversity. To measure Trp-Kyn metabolites, a LC–MS/MS metabolomics platform was employed using a targeted approach. To measure immune markers, Enzyme-linked immunosorbent assays and the Particle-enhanced turbidimetric assay was used. Results After adjusting for covariates, sCD163 (p = 0.042) and KA (p = 0.031) were higher in participants with Tat signatures N24 and R57, respectively, and amino acid variation at position 24 (adj R2 = 0.048, β = -0.416, p = 0.042) and 57 (adj R2 = 0.166, β = 0.535, p = 0.031) of Tat were associated with sCD163 and KA, respectively. Conclusions These preliminary findings suggest that amino acid variation in Tat may have an influence on underlying pathogenic HIV-1 mechanisms and therefore, this line of work merits further investigation. …

Abstract Background Cardiovascular disease is a major cause of morbidity in an aging HIV population. However, risk estimation with the most frequent equations usually classifies HIV patients as having a low or moderate risk. Several studies have described a very high prevalence of subclinical atherosclerosis in a middle-aged, non-HIV population. There is insufficient body of knowledge to understand if this is the case in people living with HIV (PLWH). We aim to calculate the proportion of patients with subclinical atherosclerosis in a single site cohort of HIV-infected subjects. Methods We have analyzed chronically HIV infected adults (≥ 18 years) who were on active follow-up in an HIV unit specialized in the care of cardiovascular health. The most recent clinical visit and vascular ultrasonography were used to assess the objectives of our research. Our primary objective was to describe the proportion of participants with subclinical atherosclerosis (focal protrusion into the lumen > 0.5 mm or > 50% of the surrounding IMT or a diffuse thickness > 1.5 mm) in a single site cohort of PLWH. Carotid and iliofemoral territories were evaluated. As a secondary objective we have run a multivariate analysis to determine which HIV and non-HIV factors might be related with the presence of atherosclerotic plaques. Findings We included a total of 463 participants between November 2017 to October 2019. Subjects were predominantly male (84.2%) with a mean age of 48.8 years (SD 10.7). Hypercholesterolemia (36%) was the most prevalent comorbidity followed by Hypertension (18%) and Hypertriglyceridemia (16%). Mean duration of HIV infection is 12.3 years. Overall, participants had been receiving cART for a median of 9.5 years. Subclinical atherosclerosis was found in 197 subjects (42.5%; CI 95% [38.0–47.2]). The disease was found more frequently in the femoral arteries (37.8%) than in the carotid vascular bed (18.6%). Despite some HIV factors correlated with the presence of plaques in a univariate analysis (e.g., time with HIV-1 RNA > 50 copies/mL or time from HIV diagnosis), the only two explanatory factors that remained associated with the presence of atherosclerotic plaques in the multivariate analysis were smoking (OR 5.47, 95% CI 3.36 – 8.90) and age (OR 1.13, 95%CI 1.10 – 1.16). Interpretation We have found a very high prevalence of subclinical atherosclerosis among our cohort of PLWH. Despite having analyzed several HIV factors, age and smoking have been found to be the only factors associated with the development of atherosclerotic plaques. …

Abstract Background Pregnancy is a critical time for women, making them more susceptible to infectious diseases like COVID-19. This study aims to determine the immunogenicity of COVID-19 in pregnant women who have been infected compared to those who have received the inactive COVID-19 vaccine. Materials and methods In this retrospective cohort study, pregnant women who received the inactivated COVID-19 vaccine (Sinopharm) and those with a history of COVID-19 infection during pregnancy were studied. Participants who had experienced stillbirth, received different COVID-19 vaccines, or had intrauterine fetal death were excluded from the study. Overall, the study included 140 participants. The participants were divided into two groups of 70 participants - pregnant women who received the Sinopharm vaccine and pregnant women who had COVID-19 infection during pregnancy. Before delivery, blood samples were collected from all mothers to evaluate the maternal immunoglobulin G (IgG) level. Blood samples were also taken from the baby’s umbilical cord during delivery to measure the newborn’s IgG level. Additionally, blood samples were collected from babies whose mothers showed signs of acute infection to measure their IgM levels and evaluate vertical transmission. Findings The study found a significant relationship between the mean level of maternal IgG and umbilical cord IgG within the groups (P 

Abstract Background Continuous monitoring of antimicrobial resistance (AMR) in Uganda involves testing bacterial isolates from clinical samples at national and regional hospitals. Although the National Microbiology Reference Laboratory (NMRL) analyzes these isolates for official AMR surveillance data, there\'s limited integration into public health planning. To enhance the utilization of NMRL data to better inform drug selection and public health strategies in combating antibiotic resistance, we evaluated the trends and spatial distribution of AMR to common antibiotics used in Uganda. Methods We analyzed data from pathogenic bacterial isolates from blood, cerebrospinal, peritoneal, and pleural fluid from AMR surveillance data for 2018–2021. We calculated the proportions of isolates that were resistant to common antimicrobial classes. We used the chi-square test for trends to evaluate changes in AMR resistance over the study period. Results Out of 537 isolates with 15 pathogenic bacteria, 478 (89%) were from blood, 34 (6.3%) were from pleural fluid, 21 (4%) were from cerebrospinal fluid, and 4 (0.7%) were from peritoneal fluid. The most common pathogen was Staphylococcus aureus (20.1%), followed by Salmonella species (18.8%). The overall change in resistance over the four years was 63–84% for sulfonamides, fluoroquinolones macrolides (46–76%), phenicols (48–71%), penicillins (42–97%), β-lactamase inhibitors (20–92%), aminoglycosides (17–53%), cephalosporins (8.3–90%), carbapenems (5.3–26%), and glycopeptides (0–20%). There was a fluctuation in resistance of Staphylococcus aureus to methicillin (60%-45%) (using cefoxitin resistance as a surrogate for oxacillin resistance) Among gram-negative organisms, there were increases in resistance to tetracycline (29–78% p 

Abstract Introduction Diarrhoea is a major public health concern in developing countries, usually exacerbated by poor water, sanitation and hygiene but its aetiology is under-studied, particularly away from capital cities. We identified diarrhoeagenic Escherichia coli (DEC) from stools collected in Ile-Ife and Ilesa, Osun state, Nigeria and determined their antibiotic resistance profiles. Methods Stool samples from 167 children with diarrhoea and 334 controls under the age of 5 years were cultured for Escherichia coli and Salmonella. Bacterial isolates were identified biochemically and DEC were identified by PCR. Antimicrobial susceptibility testing was by modified Kirby-Bauer disc diffusion method in accordance with the CLSI guidelines. Data were analyzed using Chi-square and Fisher’s exact tests. Result Diarrhoea infection is significantly high among children under 12 months (p = 0.002), caregivers without at least primary school education (p = 0.006), breastfeeding for under 6 months (p˂0.001), and caregivers who were siblings (p = 0.004). DEC was detected in 69(41.3%) cases but only 86(25.7%) controls (p 

Abstract Background Brucellosis is a global public health concern and occurs mainly in young adults and the elderly, with children having a lower incidence, thus often leading to delayed treatment. This study aimed to describe the epidemiologic features and clinical characteristics of brucellosis in children. Methods In this retrospective study, the clinical data of five children diagnosed with brucellosis in Anhui Provincial Children’s Hospital between January 1, 2021 and December 30, 2022 were analyzed. Results All five cases were from non-pastoral areas, among which three have a history of livestock exposure and originated from the countryside. All patients had medium-high grade fever, mostly accompanied by night sweats and malaise, and three had joint pains. Laboratory tests showed that their white blood cell count was normal or mildly raised, with lymphocytes as the predominant cell population. Four patients had anemia, four had aspartate aminotransferase and alanine aminotransferase abnormality, and two had elevated ferritin levels. All blood samples were positive for Brucella culture, one of which had positive bone marrow culture, and all had positive serology test results. All patients were treated with rifampicin, in combination with sulfamethoxazole or doxycycline for 6 weeks following diagnosis. Four children had a good prognosis, but one child had recurrent joint pain. Conclusions The epidemiologic history of children from non-pastoral areas with brucellosis is often unclear; clinical manifestations and laboratory tests lack specificity; and they are easily delayed diagnosis. Clinicians should remain vigilant regarding the possibility of this disease in children with fever of unknown origin. The epidemiological history should be investigated in detail to improve the diagnostic ability of brucellosis. We recommend emphasizing serological testing. Children with brucellosis who receive timely diagnosis and standardized treatment can expect a favorable prognosis. …