A common result of infection is an abnormal immune response, which may be detrimental to the host. To control the infection, the immune system might undergo regulation, therefore producing an excess ...of either pro-inflammatory or anti-inflammatory pathways that can lead to widespread inflammation, tissue damage, and organ failure. A dysregulated immune response can manifest as changes in differentiated immune cell populations and concentrations of circulating biomarkers. To propose an early diagnostic system that enables differentiation and identifies the severity of immune-dysregulated syndromes, we built an artificial intelligence tool that uses input data from single-cell RNA sequencing. In our results, single-cell transcriptomics successfully distinguished between mild and severe sepsis and COVID-19 infections. Moreover, by interpreting the decision patterns of our classification system, we identified that different immune cells upregulating or downregulating the expression of the genes CD3, CD14, CD16, FOSB, S100A12, and TCRɣδ can accurately differentiate between different degrees of infection. Our research has identified genes of significance that effectively distinguish between infections, offering promising prospects as diagnostic markers and providing potential targets for therapeutic intervention.
Archaea are a vast and unexplored cellular domain that thrive in a high diversity of environments, having central roles in processes mediating global carbon and nutrient fluxes. For these organisms ...to balance their metabolism, the appropriate regulation of their gene expression is essential. A key momentum in regulating genes responsible for the life maintenance of archaea is when transcription factor proteins bind to the promoter element. This DNA segment is conserved, which enables its exploration by machine learning techniques. Here, we trained and tested a support vector machine with 3935 known archaeal promoter sequences. All promoter sequences were coded into DNA Duplex Stability. After, we performed a model interpretation task to map the decision pattern of the classification procedure. We also used a dataset of known-promoter sequences for validation. Our results showed that an AT rich region around position - 27 upstream (relative to the start TSS) is the most conserved in the analyzed organisms. In addition, we were able to identify the BRE element (- 33), the PPE (at - 10) and a position at + 3, that provides a more understandable picture of how promoters are organized in all the archaeal organisms. Finally, we used the interpreted model to identify potential promoter sequences of 135 unannotated organisms, delivering regulatory regions annotation of archaea in a scale never accomplished before ( https://pcyt.unam.mx/gene-regulation/ ). We consider that this approach will be useful to understand how gene regulation is achieved in other organisms apart from the already established transcription factor binding sites.
The higher movement of people was one of the variables that contributed to the spread of the infectious agent SARS-CoV-2 during the COVID-19 pandemic. Governments worldwide responded to the virus by ...implementing measures that would restrict people's movements, and consequently, the spread of the disease. During the onset of the pandemic, the technology companies Apple, Google, and Meta used their infrastructure to anonymously gather mobility reports from their users.
This study aims to compare mobility data reports collected by Apple, Google, and Meta (formerly Facebook) during the COVID-19 pandemic and a major winter storm in Texas in 2021. We aim to explore the hypothesis that different people exhibit similar mobility trends during dramatic events and to emphasize the importance of this type of data for public health measures. The study also aims to promote evidence for companies to continue releasing mobility trends data, given that all 3 companies have discontinued these services.
In this study, we collected mobility data spanning from 2020 to 2022 from 3 major tech companies: Apple, Google, and Meta. Our analysis focused on 58 countries that are common to all 3 databases, enabling us to conduct a comprehensive global-scale analysis. By using the winter storm that occurred in Texas in 20201 as a benchmark, we were able to assess the robustness of the mobility data obtained from the 3 companies and ensure the integrity of our findings.
Our study revealed convergence in the mobility trends observed across different companies during the onset of significant disasters, such as the first year of the COVID-19 pandemic and the winter storm that impacted Texas in 2021. Specifically, we observed strong positive correlations (r=0.96) in the mobility data collected from different tech companies during the first year of the pandemic. Furthermore, our analysis of mobility data during the 2021 winter storm in Texas showed a similar convergence of trends. Additionally, we found that periods of stay-at-home orders were reflected in the data, with record-low mobility and record-high stay-at-home figures.
Our findings provide valuable insights into the ways in which major disruptive events can impact patterns of human mobility; moreover, the convergence of data across distinct methodologies highlights the potential value of leveraging mobility data from multiple sources for informing public health decision-making. Therefore, we conclude that the use of mobility data is an asset for health authorities to consider during natural disasters, as we determined that the data sets from 3 companies yielded convergent mobility patterns. Comparatively, data obtained from a single source would be limited, and therefore, more difficult to interpret, requiring careful analysis.
Archaea are a vast and unexplored domain. Bioinformatic techniques might enlighten the path to a higher quality genome annotation in varied organisms. Promoter sequences of archaea have the action of ...a plethora of proteins upon it. The conservation found in a structural level of the binding site of proteins such as TBP, TFB, and TFE aids RNAP-DNA stabilization and makes the archaeal promoter prone to be explored by statistical and machine learning techniques.
In this study, experimentally verified promoter sequences of the organisms Haloferax volcanii, Sulfolobus solfataricus, and Thermococcus kodakarensis were converted into DNA duplex stability attributes (i.e. numerical variables) and were classified through Artificial Neural Networks and an in-house statistical method of classification, being tested with three forms of controls. The recognition of these promoters enabled its use to validate unannotated promoter sequences in other organisms. As a result, the binding site of basal transcription factors was located through a DNA duplex stability codification. Additionally, the classification presented satisfactory results (above 90%) among varied levels of control.
The classification models were employed to perform genomic annotation into the archaea Aciduliprofundum boonei and Thermofilum pendens, from which potential promoters have been identified and uploaded into public repositories.
The onset of the COVID-19 pandemic has placed a significant burden on healthcare systems worldwide, particularly in sub-Saharan regions where healthcare resources are limited. The transmission of ...SARS-CoV-2 is facilitated by the movement of people from place to place. Therefore, implementing measures that restrict movement of people and contacts is crucial in controlling the spread of the disease. Following the identification of the first COVID-19 case in Rwanda, the government implemented stringent measures, including a complete nationwide lockdown, border closures, curfews, reduced capacity in public transportation and businesses, and mandatory testing. This study aims to assess epidemiological trends in COVID-19 cases in relation to changes in population mobility within the public transportation system.
A descriptive analysis using publicly available data on COVID-19 epidemiological indicators (cases, deaths, vaccinations, and stringency index) and mobility data was conducted.
The results reveal a strong correlation between mobility in public transportation and other activities, underscoring Rwanda's reliance on its public transportation system. The study also identifies a pattern where increases in transit station mobility preceded spikes in COVID-19 cases, suggesting that the subsequent rise in public transportation usage may contribute to higher infection rates.
Therefore, this study emphasizes the importance of ongoing vigilance and regulatory measures regarding public transportation during infectious disease outbreaks.
The overall goal of this survey was to understand the knowledge, attitudes, and practices related to the Ebola Virus Disease (EVD) in Rwanda.
This mixed-method cross-sectional survey was conducted in ...five selected districts of Rwanda. Quantitative data were collected from 1,010 participants using Kobo Collect Software and the analysis was performed using SPSS and Python software. Qualitative data were specifically collected from 98 participants through Key Informant Interviews (KIIs) and Focus Group Discussion (FGDs). Interview transcripts were imported into NVIVO 8 for coding and subsequent analysis.
As per our quantitative findings, we report that from the 1,010 respondents, 99.6% reported having previously heard of Ebola, 97.2% believed that vaccination is important in combatting the disease and 93.3% of individuals reported a willingness to receive vaccination should one become available. Around 54% of the respondents were correct in identifying that the disease is of a viral origin which originates from wild animals (42.1%). When asked if they believed that Rwanda is at risk of an EVD outbreak, 90% of the respondents believe that the country is at risk of an EVD outbreak, and the cofactors *gender* and *whether people dwell in Rubavu/Rusizi* were found to significantly impact their perception of threat. As per our qualitative findings, the respondents mentioned that both geographical proximity and relations with the Democratic Republic of Congo place Rwanda at risk of developing an internal outbreak. Although the respondents seemed to be aware of the Ebola prevention behaviours, it was noted that some of them will require significant time before reintegrating into the community an EVD survivor, as they will first need assurance that the patient has fully recovered. Therefore, the qualitative findings reinforce what we originally reported in the quantitative approach to this study.
Our results show that there was high EVD-related knowledge and awareness among the general population in Rwanda. However, for strong public health awareness, preparedness, and protection, a massive investment should always be made in education about EVD with a special focus on districts neighboring countries where the disease is consistently being reported.
After the initial onset of the SARS-CoV-2 pandemic, the government of Canada and provincial health authorities imposed restrictive policies to limit virus transmission and mitigate disease burden. In ...this study, the pandemic implications in the Canadian province of Nova Scotia (NS) were evaluated as a function of the movement of people and governmental restrictions during successive SARS-CoV-2 variant waves (i.e., Alpha through Omicron).
Publicly available data obtained from community mobility reports (Google), the Bank of Canada Stringency Index, the "COVID-19 Tracker" service, including cases, hospitalizations, deaths, and vaccines, population mobility trends, and governmental response data were used to relate the effectiveness of policies in controlling movement and containing multiple waves of SARS-CoV-2.
Our results indicate that the SARS-CoV-2 pandemic inflicted low burden in NS in the initial 2 years of the pandemic. In this period, we identified reduced mobility patterns in the population. We also observed a negative correlation between public transport (-0.78), workplace (-0.69), retail and recreation (-0.68) and governmental restrictions, indicating a tight governmental control of these movement patterns. During the initial 2 years, governmental restrictions were high and the movement of people low, characterizing a 'seek-and-destroy' approach. Following this phase, the highly transmissible Omicron (B.1.1.529) variant began circulating in NS at the end of the second year, leading to increased cases, hospitalizations, and deaths. During this Omicron period, unsustainable governmental restrictions and waning public adherence led to increased population mobility, despite increased transmissibility (26.41-fold increase) and lethality (9.62-fold increase) of the novel variant.
These findings suggest that the low initial burden caused by the SARS-CoV-2 pandemic was likely a result of enhanced restrictions to contain the movement of people and consequently, the spread of the disease. Easing public health restrictions (as measured by a decline in the BOC index) during periods of high transmissibility of circulating COVID-19 variants contributed to community spread, despite high levels of immunization in NS.
Human Mpox (formerly monkeypox) infection is an emerging zoonotic disease caused by the Mpox virus (MPXV). We describe the complete genome annotation, phylogeny, and mutational profile of a novel, ...sustained Clade I Mpox outbreak in the city of Kamituga in Eastern Democratic Republic of the Congo (DRC).
A cross-sectional, observational, cohort study was performed among patients of all ages admitted to the Kamituga Hospital with Mpox infection symptoms between late September 2023 and late January 2024. DNA was isolated from Mpox swabbed lesions and sequenced followed by phylogenetic analysis, genome annotation, and mutational profiling.
We describe an ongoing Clade I Mpox outbreak in the city of Kamituga, South Kivu Province, Democratic Republic of Congo. Whole-genome sequencing of the viral RNA samples revealed, on average, 201.5 snps, 28 insertions, 81 deletions, 2 indels, 312.5 total variants, 158.3 amino acid changes, 81.66 intergenic variants, 72.16 synonymous mutations, 106 missense variants, 41.16 frameshift variants, and 3.33 inframe deletions across six samples. By assigning mutations at the proteome level for Kamituga MPXV sequences, we observed that seven proteins, namely, C9L (OPG047), I4L (OPG080), L6R (OPG105), A17L (OPG143), A25R (OPG151), A28L (OPG153), and B21R (OPG210) have emerged as hot spot mutations based on the consensuses inframe deletions, frameshift variants, synonymous variants, and amino acids substitutions. Based on the outcome of the annotation, we found a deletion of the D14L (OPG032) gene in all six samples. Following phylogenetic analysis and whole genome assembly, we determined that this cluster of Mpox infections is genetically distinct from previously reported Clade I outbreaks, and thus propose that the Kamituga Mpox outbreak represents a novel subgroup (subgroup VI) of Clade I MPXV.
Here we report the complete viral genome for the ongoing Clade I Mpox Kamituga outbreak for the first time. This outbreak presents a distinct mutational profile from previously sequenced Clade I MPXV oubtreaks, suggesting that this cluster of infections is a novel subgroup (we term this subgroup VI). These findings underscore the need for ongoing vigilance and continued sequencing of novel Mpox threats in endemic regions.
is a family of large, complex, enveloped, and double-stranded DNA viruses. The members of this family are ubiquitous and well known to cause contagious diseases in humans and other types of animals ...as well. Taxonomically, the
family is classified into two subfamilies, namely
(affecting vertebrates) and
(affecting insects). The members of the
subfamily are further divided into 18 genera based on the genome architecture and evolutionary relationship. Of these 18 genera, four genera, namely Molluscipoxvirus, Orthopoxvirus, Parapoxvirus, and Yatapoxvirus, are known for infecting humans. Some of the popular members of
are variola virus, vaccine virus, Mpox (formerly known as monkeypox), cowpox, etc. There is still a pressing demand for the development of effective vaccines against poxviruses. Integrated immunoinformatics and artificial-intelligence (AI)-based methods have emerged as important approaches to design multi-epitope vaccines against contagious emerging infectious diseases. Despite significant progress in immunoinformatics and AI-based techniques, limited methods are available to predict the epitopes. In this study, we have proposed a unique method to predict the potential antigens and T-cell epitopes for multiple poxviruses. With PoxiPred, we developed an AI-based tool that was trained and tested with the antigens and epitopes of poxviruses. Our tool was able to locate 3191 antigen proteins from 25 distinct poxviruses. From these antigenic proteins, PoxiPred redundantly located up to five epitopes per protein, resulting in 16,817 potential T-cell epitopes which were mostly (i.e., 92%) predicted as being reactive to CD8+ T-cells. PoxiPred is able to, on a single run, identify antigens and T-cell epitopes for poxviruses with one single input, i.e., the proteome file of any poxvirus.
Post-acute sequelae of COVID-19 (PASC) or the continuation of COVID-19 (Coronavirus disease 2019) symptoms past 12 weeks may affect as many as 30% of people recovering from a SARS-CoV-2 (severe acute ...respiratory coronavirus 2) infection. The mechanisms regulating the development of PASC are currently not known; however, hypotheses include virus reservoirs, pre-existing conditions, microblood clots, immune dysregulation, as well as poor antibody responses. Importantly, virus neutralizing antibodies are essential for COVID-19 recovery and protection from reinfection but there is currently limited information on these immune regulators and associated cytokines in PASC patients. Understanding the key drivers of general and specific symptoms associated with Long COVID and the presence of virus neutralizing antibodies in PASC will aid in the development of therapeutics, diagnostics, and vaccines which currently do not exist. We designed a cross-sectional study to investigate systemic antibody and cytokine responses during COVID-19 recovery and PASC. In total, 195 participants were recruited in one of four groups: (1) Those who never had COVID-19 (No COVID); (2) Those in acute COVID-19 recovery (Acute Recovery) (4-12 weeks post infection); (3) Those who recovered from COVID-19 (Recovered) (+ 12 weeks from infection); and (4) those who had PASC (PASC) (+ 12 weeks from infection). Participants completed a questionnaire on health history, sex, gender, demographics, experiences with COVID-19 acute and COVID-19 recovery/continuing symptoms. Serum samples collected were evaluated for antibody binding to viral proteins, virus neutralizing antibody titers, and serum cytokine levels using Ella SimplePlex Immunoassay™ panels. We found participants with PASC reported more pre-existing conditions (e.g. such as hypertension, asthma, and obesity), and PASC symptoms (e.g. fatigue, brain fog, headaches, and shortness of breath) following COVID-19 than COVID-19 Recovered individuals. Importantly, we found PASC individuals to have significantly decreased levels of neutralizing antibodies toward both SARS-CoV-2 and the Omicron BA.1 variant. Sex analysis indicated that female PASC study participants had sustained antibody levels as well as levels of the inflammatory cytokines GM-CSF and ANG-2 over time following COVID-19. Our study reports people experiencing PASC had lower levels of virus neutralizing antibodies; however, the results are limited by the collection time post-COVID-19 and post-vaccination. Moreover, we found females experiencing PASC had sustained levels of GM-CSF and ANG-2. With lower levels of virus neutralizing antibodies, this data suggests that PASC individuals not only have had a suboptimal antibody response during acute SARS-CoV-2 infection but may also have increased susceptibility to subsequent infections which may exacerbate or prolong current PASC illnesses. We also provide evidence suggesting GM-CSF and ANG-2 to play a role in the sex-bias of PASC. Taken together, our findings maybe important for understanding immune molecular drivers of PASC and PASC subgroups.
