In this image, the autors reinterprate \"The Thinker\" from Auguste Rodin to transfer knowledge about dengue fever, which can range from flu-like illness to severe hemorrhagic fever. By fostering awareness and understanding of dengue fever, we strive to empower individuals and communities in the ongoing fight against dengue and other infectious threats.

BACKGROUND: The genetic susceptibility association between viral infection and the risk of colorectal cancer (CRC) has not been established.
METHODS: We conducted two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data. In addition to traditional MR methods, we employed several other approaches, including cML, ConMix, MR-RAPS, and dIVW, to comprehensively assess causal effects. Sensitivity analyses were also performed to ensure the robustness of the results.
RESULTS: After sensitivity analysis, presence of SNPs linked to increased susceptibility to cold sores infection was found to decrease the risk of CRC (OR: 0.73, 95% CI: 0.57-0.93, P = 0.01). In subgroup analysis, presence of SNPs linked to increased susceptibility to viral hepatitis (OR: 0.89, 95% CI: 0.81-0.98, P = 0.02) and infectious mononucleosis (OR: 0.91, 95% CI: 0.84-0.98, P = 0.02) were associated with a decreased risk of colon cancer, while measles virus (OR: 1.41, 95% CI: 1.07-1.85, P = 0.01) was associated with an increased risk of colon cancer. Presence of SNPs linked to increased susceptibility to herpes zoster (OR: 1.26, 95% CI: 1.05-1.52, P = 0.01) was associated with an increased risk of rectal cancer, while infectious mononucleosis (OR: 0.809, 95% CI: 0.80-0.98, P = 0.02) was associated with a decreased risk.
CONCLUSIONS: The study provides the first evidence of the genetic susceptibility associations between different viral infections and CRC, enhancing our understanding of the etiology of CRC.

As autologous stem cell transplantation (ASCT) is increasingly frequent in some patients with multiple sclerosis (MS), the knowledge of its adverse effects is paramount. Early complications (within 30 from transplantation) are usually due to conditioning regimen and consequent neutropenia. They include infections and noninfectious complications, such as oral and intestinal mucositis, increases in liver enzymes, hemorrhagic cystitis, and worsening of neurologic symptoms. Infections in the early phase, particularly during neutropenia, are mainly of bacterial origin, such as bloodstream infections, pneumonia, central-venous catheter-related infections, urinary infections, and neutropenic typhlitis, followed by viral reactivations. Prophylaxis with acyclovir against reactivation of herpes simplex virus (HSV) and varicella-zoster virus (VZV) is recommended, while a preemptive strategy is used for cytomegalovirus (CMV) and Epstein-Barr virus (EBV) management. Fungal infections are infrequent and mainly caused by Candida, thus fluconazole prophylaxis is used in some centers. Late complications include secondary autoimmune diseases: hematologic, such as immune thrombocytopenic purpura, autoimmune hemolytic anemia, or acquired hemophilia, or nonhematologic, such as thyroiditis, rheumatoid arthritis, or Crohn\'s disease. Other late complications are endocrinopathies and gonadal dysfunction with possible consequences on fertility. Particularly in women over 32 years of age, the risk of infertility and premature ovarian insufficiency can be significant. Thus, reproductive counseling with fertility preservation techniques if required is mandatory before ASCT.

Viral infections and associated illnesses account for approximately 3.5 million global fatalities and public health problems. Medicinal plants, with their wide therapeutic range and minimal side effects, have gained limelight particularly in response to growing concerns about drug resistance and sluggish development of antiviral drugs. This study computationally assessed 11 chemical compounds from Berberis lycium along with two antiviral drugs to inhibit SARS CoV 2 (coronavirus disease 2019 [COVID-19]) RNA-dependent RNA polymerase (RdRP), influenza virus RdRP, and two crucial dengue virus (DENV) enzymes (NS2B/NS3 protease and NS5 polymerase). Berberine and oxyberberine passed all pharmacokinetics analysis filters including Lipinski rule, blood-brain barrier permeant, and cytochrome suppression and demonstrated drug-likeness, bioavailability, and a non-toxic profile. Docking of phytochemicals from B lycium returned promising results with selected viral proteins, ie, DENV NS2BNS3 (punjabine -10.9 kcal/mol), DENV NS5 (punjabine -10.4 kcal/mol), COVID-19 RdRP (oxyacanthine -9.5 kcal/mol), and influenza RdRP (punjabine -10.4 kcal/mol). The optimal pharmacokinetics of berberine exhibited good binding energies with NS2BNS3 (-8.0 kcal/mol), NS5 (-8.3 kcal/mol), COVID RdRP (-7.7 kcal/mol), and influenza RdRP (-8.3 kcal/mol), while molecular dynamics simulation of a 50-ns time scale by GROMACS software package provided insights into the flexibility and stability of the complexes. A hidden treasure trove for antiviral research, berberine, berbamine, berbamunine, oxyberberine, oxyacanthine, baluchistanamine, and sindamine has showed encouraging findings as possible lead compounds. Pharmacological analyses provide credence for the proposed study; nevertheless, as the antiviral mechanisms of action of these phytochemicals are not well understood, additional research and clinical trials are required to demonstrate both their efficacy and toxicity through in vitro and in vivo studies.

Drug resistance of pathogens, including viruses, is one of the reasons for decreased efficacy of therapy. Considering the impact of HIV type 1 (HIV-1) on the development of progressive immune dysfunction and the rapid development of drug resistance, the analysis of HIV-1 resistance is of high significance. Currently, a substantial amount of data has been accumulated on HIV-1 drug resistance that can be used to build both qualitative and quantitative models of HIV-1 drug resistance. Quantitative models of drug resistance can enrich the information about the efficacy of a particular drug in the scheme of antiretroviral therapy. In our study, we investigated the possibility of developing models for quantitative prediction of HIV-1 resistance to eight protease inhibitors based on the analysis of amino acid sequences of HIV-1 protease for 900 virus variants. We developed random forest regression (RFR), support vector regression (SVR), and self-consistent regression (SCR) models using binary vectors containing values from 0 or 1, depending on the presence of a specific peptide fragment in each amino acid sequence as independent variables, while fold ratio, reflecting the level of resistance, was the predicted variable. The SVR and SCR models showed the highest predictive performances. The models built demonstrate reasonable performances for eight out of nine (R2 varied from 0.828 to 0.909) protease inhibitors, while R2 for predicting tipranavir fold ratio was lower (R2 was 0.642). We believe that the developed approach can be applied to evaluate drug resistance of molecular targets of other viruses where appropriate experimental data are available.

Macrophage activation syndrome (MAS) is a life-threatening systemic hyperinflammatory syndrome triggered by various infections, particularly viral infections, autoimmune disorders, and malignancy. The condition is characterized by an increased production of proinflammatory cytokines resulting in a cytokine storm and has been associated with poor clinical outcomes. During the COVID-19 pandemic, patients with severe manifestations developed features similar to those of MAS, although these characteristics remained well defined within the lung. Additionally, other viral infections including EBV, the herpes family of viruses, hepatitis viruses, influenza, HIV, and hemorrhagic fevers can be complicated by MAS. The diagnosis and management of the condition remain challenging due to the lack of consensus on specific guidelines, especially among the adult population. Currently, therapeutic options primarily rely on medications that are typically used to treat primary hemophagocytic lymphohistiocytosis, such as corticosteroids and etoposide. In addition, cytokine-targeted therapies present promising treatment options. The objective of this review is to discuss the emergence of MAS in the context of viral infections including, but not limited to, its occurrence in COVID-19.

BACKGROUND: Otic involvement is common in children during acute infectious diseases, and is an important cause of morbidity and health service utilization.
METHODS: We performed a retrospective analysis of pediatric cases hospitalized in the largest infectious disease hospital in Romania between 2018 and 2023, with the aim of quantifying the incidence and impact of acute otitis (AO) according to pediatric age subgroups.
RESULTS: A total of 1118 cases diagnosed with AO were eligible and included in the analysis. Acute congestive otitis media was the most common subtype, identified in 53.3% of cases, followed by acute purulent otitis media (APOM) in 26.7% of children. The majority of AO cases (69.9%) were diagnosed in the pre-pandemic period (2018-2019), and infants (10.6%), toddlers (49.4%), and preschoolers (29.2%) were the most affected age groups. A viral infection associated with the AO episode was documented in 49.6% of cases. Influenza viruses were most commonly reported (20.5%), followed by SARS-CoV-2 (5.8%), and adenovirus (4.9%). A total of 38 cases of AO were identified in children with measles. In 15.9% of APOM cases, Streptococcus pneumoniae was isolated by culture from otic secretions. The duration of hospitalization was longer in children with APOM and acute otitis externa compared to the other subtypes of AO (p < 0.001).
CONCLUSIONS: Our study highlights the importance of ENT (ear, nose, and throat) monitoring in children hospitalized for acute infectious diseases, as the majority of AO cases occur in the context of a viral infection. These findings emphasize the necessity for tailored assessment and intervention in suspected cases of AO, especially in young children under 5 years of age.

UNASSIGNED: Longitudinal data on how acute respiratory illness (ARI) affects behavior, namely school or work participation, and nonpharmaceutical intervention (NPI) usage before and during the COVID-19 pandemic is limited. The authors assessed how ARIs and specific symptoms affected school, work, and health-related behaviors over time.
UNASSIGNED: From November 2019 to June 2021, participating households with children in King County, Washington, were remotely monitored for ARI symptoms weekly. Following ARIs, participants reported illness-related effects on school, work, and NPI use. Using logistic regression with generalized estimating equations, the authors examined associations between symptoms and behaviors.
UNASSIGNED: Of 1,861 participants, 581 (31%) from 293 households reported 884 ARIs and completed one-week follow-up surveys. Compared with the prepandemic period, during the period of the pandemic pre-COVID-19 vaccine, ARI-related school (56% vs 10%, p<0.001) absenteeism decreased and masking increased (3% vs 28%, p<0.001). After vaccine authorization in December 2020, more ARIs resulted in masking (3% vs 48%, p<0.001), avoiding contact with non-household members (26% vs 58%, p<0.001), and staying home (37% vs 69%, p<0.001) compared with the prepandemic period. Constitutional symptoms such as fever were associated with work disruptions (OR=1.91; 95% CI=1.06, 3.43), staying home (OR=1.55; 95% CI=1.06, 2.27), and decreased contact with non-household members (OR=1.58; 95% CI=1.05, 2.36).
UNASSIGNED: This remote household study permitted uninterrupted tracking of behavioral changes in families with children before and during the COVID-19 pandemic, identifying increased use of some NPIs when ill but no additional illness-associated work or school disruptions.

OBJECTIVE: Recent large-scale epidemiological studies have revealed significant temporal associations between certain viral infections and the subsequent development of Kawasaki disease (KD). Despite these associations, definitive laboratory evidence linking acute or recent viral infections to KD cases remains elusive. The objective of this study is to employ a molecular epidemiological approach to investigate the temporal association between viral infections and the development of KD.
METHODS: We analyzed 2460 patients who underwent the FilmArray® Respiratory Panel test between April 2020 and September 2021.
RESULTS: Following the application of inclusion criteria, 2402 patients were categorized into KD (n = 148), respiratory tract infection (n = 1524), and control groups (n = 730). The KD group exhibited higher positive rates for respiratory syncytial virus (RSV), human rhinovirus/enterovirus (hRV/EV), parainfluenza virus (PIV) 3, and adenovirus (AdV) compared to the control group. Additionally, coinfections involving two or more viruses were significantly more prevalent in the KD group. Notably, RSV-positive, hRV/EV-positive, and PIV3-positive KD patients exhibited a one-month delay in peak occurrence compared to non-KD patients positive for corresponding viruses. In contrast, AdV-positive KD cases did not show a one-month delay in peak occurrence. Moreover, anti-RSV, anti-PIV3, and anti-AdV antibody-positive rates or antibody titers were higher in RSV-, PIV3-, and AdV-positive KD cases, respectively, compared to non-KD cases with the same viral infections.
CONCLUSIONS: Recent infection with RSV, PIV3, or AdV, occasionally in conjunction with other viruses, may contribute to the pathogenesis of KD as infrequent complications.

BACKGROUND: The organism-wide effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection are well studied, but little is known about the dynamics of how the infection spreads in time among or within cells due to the scarcity of suitable high-resolution experimental systems. It has been reported that SARS-CoV-2 infection pathways converge at calcium influx and subcellular calcium distribution changes. Imaging combined with a proper staining technique is an effective tool for studying subcellular calcium-related infection and replication mechanisms at such resolutions.
METHODS: Using two-photon (2P) fluorescence imaging with our novel Ca-selective dye, automated image analysis and clustering analysis were applied to reveal titer and variant effects on SARS-CoV-2-infected Vero E6 cells.
RESULTS: The application of a new calcium sensor molecule is shown, combined with a high-end 2P technique for imaging and identifying the patterns associated with cellular infection damage within cells. Vero E6 cells infected with SARS-CoV-2 variants, D614G or B.1.1.7, exhibit elevated cytosolic calcium levels, allowing infection monitoring by tracking the cellular changes in calcium level by the internalized calcium sensor. The imaging provides valuable information on how the level and intracellular distribution of calcium are perturbed during the infection. Moreover, two-photon calcium sensing allowed the distinction of infections by two studied viral variants via cluster analysis of the image parameters. This approach will facilitate the study of cellular correlates of infection and their quantification depending on viral variants and viral load.
CONCLUSIONS: We propose a new two-photon microscopy-based method combined with a cell-internalized sensor to quantify the level of SARS-CoV-2 infection. We optimized the applied dye concentrations to not interfere with viral fusion and viral replication events. The presented method ensured the proper monitoring of viral infection, replication, and cell fate. It also enabled distinguishing intracellular details of cell damage, such as vacuole and apoptotic body formation. Using clustering analysis, 2P microscopy calcium fluorescence images were suitable to distinguish two different viral variants in cell cultures. Cellular harm levels read out by calcium imaging were quantitatively related to the initial viral multiplicity of infection numbers. Thus, 2P quantitative calcium imaging might be used as a correlate of infection or a correlate of activity in cellular antiviral studies.