Journal of Infection and Public Health

Introduction Aspiration events in hospitalized adults are common and linked to substantial morbidity, mortality, and healthcare burden. While antiemetics have been studied for aspiration prevention in specific settings, evidence for their broader preventive use in hospitalized adults is limited. We conducted a systematic review and meta-analysis to evaluate the effect of prophylactic scheduled antiemetics on aspiration events in adult inpatients. Methods: Ovid MEDLINE, Ovid Embase, CINAHL, and Cochrane Library (via Wiley) were searched in May 2025. We included randomized controlled trials (RCTs) and observational studies assessing prophylactic scheduled antiemetic use in hospitalized adults, with aspiration events as the primary outcome. Secondary outcomes were aspiration pneumonia, hospital length of stay, increased oxygen requirement, ICU admission, and mortality. Two investigators screened and independently extracted data in duplicate using standardized data collection forms. Extracted information included study characteristics, patient demographics and clinical characteristics, interventions, and outcomes. Results: Three RCTs met inclusion criteria (n = 515 patients; 237 antiemetic, 278 placebo). Pooled analysis of two RCTs demonstrated an 88% relative risk [RR] reduction of aspiration events; (2.8% [3/106] prophylactic antiemetic vs 27.9% [29/104] placebo; RR = 0.12, 95% confidence intervals [CI]: 0.02-0.73, p <0.0001, low certainty) in the antiemetic group. Pneumonia rates were also lower in the antiemetic group although they did not reach statistical significance (16.5% vs 32.4%; RR 0.44, 95% CI 0.15-1.28, P = 0.13, low certainty). ICU admission rates were lower in the antiemetic group (2.6% [2/76]) vs. placebo (23% [17/74]); RR = 0.11, 95% CI: 0.03-0.48, p=0.003, very low certainty). Mortality was similar between groups (35.0% vs 38.1%; RR 1.02, 95% CI: 0.84-1.24, P = 0.85, low certainty). No adverse events were reported among all studies. Conclusion: Prophylactic scheduled antiemetics were associated with a significant reduction in aspiration and ICU admission. There was a non-significant but favorable trend towards reduction of pneumonia among hospitalized adults. Larger, high-quality trials are needed to clarify their role in aspiration prevention.

Praziquantel, which has limited efficacy against young parasites and reduces susceptibility, is the principal therapy for schistosomiasis, a neglected tropical illness. This work identified fungal-derived compounds with potential dual inhibitory action against Schistosoma mansoni DHODH and cathepsin B1 using an integrated computational method. From 1,831 fungal metabolites, 120 were selected for molecular docking after structure standardisation, drug-likeness evaluation, ADMET, and toxicity screening. Ganoderlactone B (CID_122184973) and Spiroapplanatumine F (CID_132962217) strongly bound to DHODH and CB1, with docking affinities of -10.6 and -10.0 kcal/mol and -9.0 and -8.9, respectively. Docking validation showed good discrimination between active compounds and decoys with area-under-the-curve values of 0.98 for DHODH and 0.96 for CB1. The protein-ligand interaction study showed hydrogen bonding, hydrophobic interactions, and van der Waals contacts at the binding sites. In 100 ns molecular dynamics simulations, protein complexes exhibited modest backbone deviations and maintained compactness, although CID_132962217 showed sustained binding and a constrained conformation. MM-PBSA analysis identified CID_122184973 as the best common ligand for both targets. At the B3LYP/6-31G level, density functional theory calculations showed that CID_139584993 had the lowest HOMO-LUMO energy gap and hardness values of 3.552 and 1.776 eV, respectively, and the highest softness value of 0.282 eV-1, indicating greater electronic reactivity. Electrostatic potential mapping and QSAR predictions supported their interaction and antiparasitic potential. Overall, CID_122184973 and CID_132962217 are promising fungal scaffolds for dual-target anti-schistosomal drug development. Experimental enzyme inhibition, parasite viability, toxicity, and in vivo research are needed to confirm computational findings.

Post Acute Sequelae of SARS CoV 2 infection, or PASC, is an emerging public health concern. Longitudinal data from South Asia remain limited and the burden of persistent symptoms in Pakistan is not well characterized. This study examined the long term clinical course of PASC and its relationship with fecal viral shedding and serotonin levels over a 12 month follow up period. We conducted a prospective longitudinal study of individuals with PASC. Participants underwent serial assessments of clinical symptoms, stool SARS CoV 2 RNA detection, and serum serotonin measurements. A symptom score was developed using 22 symptoms reported by more than 30 percent of participants. Participants were predominantly female with 60 percent female participation and a mean age of 42.1 years. Overall, 66 percent were overweight or obese and 23 percent reported multiple SARS CoV 2 reinfections. Symptom burden decreased significantly at 9 months and 12 months compared with baseline. Despite overall improvement, several symptoms persisted. Myalgia remained common, increasing slightly from 60 percent at baseline to 63 percent at 12 months. Musculoskeletal symptoms remained stable at approximately 60 percent. Neurocognitive symptoms declined from 40 percent to 31.3 percent, whereas psychological symptoms increased slightly from 40 percent to 45.8 percent. Fecal viral shedding was detected in 50 percent of participants and demonstrated intermittent or persistent patterns. Significant associations between fecal shedding and symptoms emerged at 6 months, particularly breathlessness, fatigue, weakness, and joint pain. Serotonin levels were comparable to those reported during acute COVID 19 infection. PASC symptoms including myalgia, joint pain, weakness, and fatigue persisted for up to one year after infection. The association between ongoing fecal viral shedding and persistent symptoms suggests that viral persistence and sustained physiological disturbances may contribute to Long COVID pathogenesis in a subset of individuals.

This study aims to identify potential inhibitors of the Ag85C enzyme from Mycobacterium tuberculosis through primary docking, pharmacophore modelling, and ADME/pharmacokinetics analysis. Delamanid and Pretomanid emerged as the top hits in primary docking, demonstrating strong binding affinities and interactions with key active site residues. A robust pharmacophore model was developed, identifying essential features for binding and used to screen 4254 antituberculotic compounds, yielding three promising candidates: F0314-0040, F0398-0505, and F0349-2716. These compounds exhibited high binding affinities in major docking studies. ADME and pharmacokinetics analysis revealed favorable Drug likeness and absorption profiles, supporting their potential as effective antituberculotic agents. The integration of computational methods provided a comprehensive approach for rational drug design.

Cancer is a serious public health problem, and is becoming more common, with a projected increase in deaths and more than 25 million new cases in coming decades. A number of molecular mechanisms are involved in the tumoral process, with one of them, never in mitosis A-related kinase 2 (NEK2), a serine/threonine protein kinase, being a frequent target of amplification in various malignancies that is responsible for chromosomal instability, aneuploidy and activation of several oncogenic pathways. Available kinase inhibitors are not yet optimized in terms of their pharmacokinetic properties for clinical use, and current therapies, such as chemotherapeutic agents or immunotherapies are often limited by their resistance. In silico methods represent an effective tool to search for novel potent inhibitors, before testing in animals, with time constraints and limited resources. To find new inhibitors of NEK2, we used E pharmacophore-based modeling and structure based virtual screening in this study. NEK2 was chosen as the target for therapeutic intervention and an energy optimized pharmacophore model was employed to screen the Enamine REAL library of millions of compounds. Pharmacodynamic and Pharmacokinetic properties of the Top hits were tested using ADMET profiling. These were further screened using molecular docking (standard precision and extra precision) and virtual screening to obtain three lead compounds 1, 2, and 3 which have docking score of -7.414, -8.037 and -7.562 respectively. MM-GBSA calculations were used to estimate the binding free energies for these complexes, which were determined to be -54.92, -54.18 and -49.23 kcal/mol. Lastly, 100 ns molecular dynamics simulations have been run to evaluate complex stability in dynamic situations. The overall results of the MD showed the overall stability of the NEK2-ligand complexes, and thus these three compounds are promising NEK2 inhibitor candidates and could be further validated in vitro and in vivo for clinical application. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=133 SRC="FIGDIR/small/742111v1_ufig1.gif" ALT="Figure 1"> View larger version (70K): org.highwire.dtl.DTLVardef@14e9cfeorg.highwire.dtl.DTLVardef@24ec78org.highwire.dtl.DTLVardef@20be75org.highwire.dtl.DTLVardef@1b80c02_HPS_FORMAT_FIGEXP M_FIG C_FIG

Sepsis is a global health problem. Patients in the Intensive Care Unit (ICU) are at risk of having sepsis because of their vulnerability and use of invasive medical devices. Emerging antimicrobial-resistance complicates treatment. Understanding bacterial profiles and antibiotic sensitivity patterns in the ICU plays an important role in managing sepsis, optimizing antimicrobial use, and improving patient outcomes. The aim of this study was to show bacterial profiles and antibiotic sensitivity patterns among patients who were admitted to the ICU at Mbeya Zonal Referral Hospital for 12 months. This was a prospective cross-sectional study among 187 sepsis-suspected patients. Data analysis was performed using SPSS Version 27. Categorical data were summarized by frequency and percentage. Fishers exact test, chi-square test, and modified Poisson regression were used to show the association between patients clinical variables and culture positivity at a 95% CI. Statistical significance was set at a p-value < 0.05. Out of 187 samples, 41.7% were culture positive. Gram-negative bacteria were commonly isolated (65.4%, with Klebsiella pneumoniae and Escherichia coli being commonly isolated. Commonly isolated Gram-positive bacteria were Coagulase-negative Staphylococcus species (19%). 100% of gram-positive bacteria and 96% of gram-negative bacteria were Multi-Drug Resistant (MDR), respectively. In multivariable analysis, patients who were intubated and mechanically ventilated (aPR = 2.208, 95% CI: 1.133-4.305, p = 0.020) and post-laparotomy patients (aPR = 3.241,95% CI: 1.320-7.958, p = 0.010) independently had a higher proportion of Gram-negative bacteria. The study reveals a high level of resistance to commonly used antimicrobials in our setting, necessitating strengthening of the antimicrobial stewardship program and routine surveillance of antimicrobial resistance patterns.

Background: Critical illness is a major contributor to morbidity and mortality in low-resource settings, yet data on its prevalence, location, management, and contextual barriers to care outside intensive care units remain limited in Ethiopia. This study aimed to determine the burden of critical illness, patient outcomes, Essential Emergency and Critical Care (EECC) provision, and barriers to implementation. Methods: This prospective mixed-methods multicenter study was conducted across 12 public hospitals in Ethiopia. A quantitative point prevalence survey assessed all adult inpatients ([&ge;]18 years) on a single census day per site using standardized vital sign criteria for critical illness. Patients were followed for 7-day in-hospital mortality, and hospital EECC resource availability was evaluated. A complementary qualitative component consisting of five key informant interviews and one focus group discussion was conducted with healthcare professionals to explore barriers to EECC implementation. Thematic analysis was used for qualitative data. Results: Of 1,077 hospitalized patients, 221 (20.5%) were critically ill. Most critically ill patients (62.0%) were managed in general wards. The 7-day in-hospital mortality was 14.0% among critically ill patients compared to 2.8% in non-critically ill patients. Only 1.8% of critically ill patients received all indicated EECC treatments. Median hospital EECC resource availability was 70.9% (IQR 41.4-79.1%), with no hospital fully equipped across all domains. Qualitative analysis identified seven major themes: challenges in early identification, resource constraints, knowledge gaps, attitudes toward EECC, organizational barriers, staff motivation issues, and delays in timely care delivery. Independent predictors of mortality included male sex, hypertension, cancer, HIV/AIDS, other comorbidities, and presence of critical illness. Conclusion: This critical illness outcome study in Ethiopia demonstrates that one in five hospitalized patients is critically ill, predominantly managed in general wards, with high short-term mortality and profound gaps in basic EECC delivery. Qualitative findings highlight multiple interconnected barriers to effective EECC implementation. Strengthening decentralized EECC through training, resource provision, ward-level protocols, and addressing systemic barriers is urgently needed to improve outcomes in resource-limited settings. Keywords: Essential Emergency Critical Care (EECC), Critical illness, Point prevalence, Mortality, Ethiopia.

Background. The clinical course of coronavirus disease 2019 (COVID-19), and the ability to anticipate which patients will require intensive care, were poorly characterized in Central Asia during the first pandemic wave. We aimed to describe the clinical features of hospitalized COVID-19 patients at the Tashkent State Medical University, Uzbekistan, and to identify risk factors for intensive care unit (ICU) admission. Methods. In this single-centre cross-sectional study, we reviewed the records of 2500 consecutive patients hospitalized between 11 April and 8 August 2020. Patients were grouped as asymptomatic or symptomatic, and symptomatic patients were compared by ICU versus non-ICU status. Groups were compared with chi-square or Fisher's exact and Mann-Whitney U tests. Univariable and multivariable logistic regression identified risk factors for ICU admission. Results. Of 2500 patients (median age 36 years; 60.9% male), 989 (39.6%) were asymptomatic and 1511 (60.4%) symptomatic. In total, 129 (5.2%) were admitted to the ICU and 38 (1.5%) died. ICU patients were older (median 56 vs 40.5 years) and more often had bilateral pneumonia, oxygen desaturation and cardiometabolic comorbidity. In the multivariable model (AUC 0.82), the independent predictors of ICU admission were ischemic heart disease (aOR 4.20), shortness of breath (aOR 3.22), hypertensive heart disease (aOR 2.93) and male sex (aOR 2.00). Conclusions. Older age, cardiometabolic comorbidity and respiratory compromise identified patients at high ICU risk. As one of the first clinical COVID-19 descriptions from Uzbekistan, these data provide a baseline for preparedness in Central Asia.

It is essential to experimentally evaluate antiviral efficacy predicted by molecular docking and related in silico approaches, which this study achieves for three bisphosphonates (alendronate, minodronate, zoledronate) and treprostinil, identified as potential antiviral therapies in our previous work. These investigational compounds had no detectable cytotoxicity at concentrations up to 25M in Vero E6 cells but also failed to show any antiviral effect against the PQ.8.1 isolate of SARS-CoV-2, when compared to control drugs (ensitrelvir, nirmatrelvir, and remdesivir). It appears that for bisphosphonates, any protective effect is likely due to other virus- or host-mediated mechanisms of action. This study demonstrates the importance of iterating between theoretical hypotheses and experiments to elucidate underlying mechanisms at play.

Purpose: To investigate the incidence, clinical features, and risk factors for SARS-CoV-2 nucleic acid re-positivity in recovered COVID-19 patients. Methods: We enrolled 441 convalescent COVID-19 patients from the rehabilitation ward of the Fifth Hospital of Shijiazhuang between January and April 2021. Based on nucleic acid test results, patients were categorized into repositive (n = 69) and non-repositive (n = 372) groups. Demographic, clinical, laboratory, and imaging data were compared between groups. Logistic regression was used to identify factors associated with re-positivity. Results: The overall re-positivity rate was 15.65%. Compared with the non-repositive group, the repositive group presented with a significantly higher proportion of moderate disease severity (72.46% vs. 50.54%) and a lower proportion of patients under 14 years old (7.25% vs. 23.66%). Additionally, multi-lobar involvement ([&ge;] 3 lobes) during the acute phase was more common in the repositive group (43.48% vs. 26.61%), with all differences being statistically significant (P < 0.001). Laboratory analysis revealed that repositive patients had significantly lower lymphocyte and eosinophil counts, as well as reduced albumin (ALB), aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, and albumin/globulin (A/G) ratio. Furthermore, circulating CD3+, CD4+, and CD8+ T-cell counts were markedly decreased. In contrast, the neutrophil-to-lymphocyte ratio (NLR), immunoglobulin M (IgM), immunoglobulin A (IgA), and neutralizing antibody (NAb) levels were significantly elevated in re-positive patients (all P < 0.05). Multivariate logistic regression analysis identified the CD8+ as independent risk factors for re-positivity. Conclusion: In convalescent patients, SARS-CoV-2 RNA re-positivity correlates with distinct clinical and immunological characteristics. The CD8+ T-cell level is an independent predictor, highlighting that dysregulated immune and inflammatory responses contribute to delayed viral clearance.

The Dengue virus (DENV), a major global health concern, causes dengue fever, predominantly affecting tropical and subtropical regions. The NS2B-NS3 protease complex of DENV is critical for viral replication, making it a promising target for antiviral drug development. This study investigates the structural dynamics of the NS2B-NS3 protease under varying pH conditions, integrating experimental and computational approaches. The recombinant NS2B-NS3 protease was expressed in E. coli, purified using affinity chromatography, and analysed for purity via SDS-PAGE. Circular dichroism (CD) spectroscopy revealed pH-dependent secondary structural changes, indicating stability at neutral to slightly basic pH and destabilization under acidic and highly basic conditions. Dynamic light scattering (DLS) analysis demonstrated protein aggregation and structural heterogeneity under extreme pH levels. Complementary in silico techniques, including homology modelling and molecular dynamics (MD) simulations, provided detailed insights into the conformational changes of the protease. The modelled structure, validated and refined through computational tools, revealed structural stability at physiological pH, with notable disruptions at pH extremes. DSSP (Dictionary of Secondary Structure of Proteins) and principal component analyses highlighted significant secondary structural transitions, especially at acidic pH where -helices and {beta}-sheets transformed into random coils Docking and MD simulation was carried out with the small molecule for therapeutic analysis between Dengue NS2bNS3 and small molecule. This study emphasizes the pH-dependent conformational plasticity of the NS2B-NS3 protease, contributing to the understanding of its functional mechanisms and providing a foundation for the rational design of pH-specific inhibitors. These findings underscore the importance of structural biology in advancing therapeutic strategies against dengue fever.

Low pathogenic avian influenza A(H7N7) virus detected in a poultry worker in Taiwan, 2026 was related to viruses circulating in Asian wild birds and possessed PB2 E627K, a mammalian adaptation marker. Enhanced surveillance for H7 viruses in poultry and rapid characterization of human cases are essential to assess pandemic potential.

Aims: To estimate the preventable pneumococcal disease burden by 21-valent pneumococcal conjugate vaccine (PCV21) compared to PCV20 for the national immunization program for adults aged 65 years or older in Japan. Methods: Serotype distribution among isolates and the annual incidence of invasive pneumococcal disease (IPD) in adults were monitored. The numbers of IPD or pneumococcal community-acquired pneumonia (pCAP) cases preventable by immunization with PCV20 or PCV21 were estimated according to reported vaccine efficacy and duration of protection in older adults. Data from our nationwide study of adult IPD surveillance and a multicenter study of pCAP were used. Results: The mean annual incidence of adult patients with IPD caused by all serotypes among adults aged [&ge;]65 years, which declined during the COVID-19 pandemic period, recovered to 89% of the pre-pandemic level in 2025. During 2023-2025, the proportion of PCV20-non-PCV21 serotypes was 8.5% for adults aged [&ge;]65 years. At the current vaccination coverage rate of 40%, the numbers of preventable IPD cases (per person per year) by PCV20 and PCV21 were 36 and 53, respectively. The preventable numbers of pCAP cases by PCV20 and PCV21 were 2,821 and 4,765, respectively. The estimated number of preventable pCAP cases was approximately 80-90 times higher than that of preventable IPD cases. Conclusion: Our data indicate that PCV21 could prevent 1.5-1.7 times as many pneumococcal disease cases as PCV20 among adults aged [&ge;] 65 years in Japan. However, PCV20 should be considered if the incidence of adult IPD cases caused by PCV20-non-PCV21 serotypes increases.

Background: Drug-resistant tuberculosis (DR-TB) remains a major challenge to tuberculosis control in sub-Saharan Africa. Cameroon faces substantial challenges in managing DR-TB; however, national evidence on treatment outcomes remains unsynthesized. This systematic review and meta-analysis aimed to estimate pooled treatment outcomes, adverse drug events (ADEs), and predictors of unfavorable outcomes among patients with DR-TB in Cameroon. Methods: This systematic review and meta-analysis followed the PRISMA 2020 guidelines. PubMed, Scopus, Embase, Web of Science, the Cochrane Library, African Journals Online. Google Scholar and reference lists were also searched. Studies reporting World Health Organization-defined treatment outcomes among patients with DR-TB were included. Random-effects meta-analyses using generalized linear mixed models with logit transformation were performed. Heterogeneity was assessed using the I2 statistic, and publication bias and sensitivity analyses were conducted. Results: Fifteen studies conducted between 1998 and 2022 were included. The pooled mortality rate was 6.8% (95% CI: 4.7-9.7; 14 reports; n = 2,351 participants), loss to follow-up was 4.1% (95% CI: 2.8-6.1; 12 studies; n = 2,244 participants), and treatment failure was 5.0% (95% CI: 1.1-19.8; 12 studies; n = 2,050 participants). The pooled treatment success rate was 74.2% (95% CI: 60.4-84.4; 13 reports; n = 2,146 participants). Treatment success improved over time and was higher with modified regimens (87.2%; 95% CI: 83.8-89.9; 3 studies; n = 460 participants) than with standard regimens (68.8%; 95% CI: 52.2-81.6; 10 studies; n = 1,686 participants). Among patients with multidrug-resistant-TB, the pooled prevalence of adverse drug events was 70.8% (95% CI: 40.2-89.7; 3 studies; n = 251 participants), with ototoxicity (41.9%; 95% CI: 23.7-62.6; 3 studies; n = 251 participants) and gastrointestinal disorders (40.9%; 95% CI: 25.5-58.2; 2 studies; n = 172 participants) being the most common events. HIV co-infection was significantly associated with unfavorable treatment outcomes (pooled OR = 2.76; 95% CI: 1.95-3.93; 6 studies), and male gender was also associated with increased odds of unfavorable outcomes (OR = 1.73; 95% CI: 1.25-2.40; 5 studies). Conclusions: Approximately three-quarters of patients with DR-TB in Cameroon achieved successful treatment, although mortality, treatment failure, and adverse drug events remain important concerns. Strengthening pharmacovigilance, integrated TB/HIV care, and the implementation of effective all-oral regimens are essential to improve treatment outcomes. Systematic review registration number: CRD420261404490.

Background: Hepatitis E virus (HEV) is highly endemic in several African countries with high mortality rate among pregnant women. The prevalence of HEV in Niger among pregnant women is unknown. We hereby aim to report the prevalence and risk factors of HEV among pregnant women in Niamey, Niger. Methods: Blood samples were collected from pregnant women attending antenatal consultation in three selected Health centers in Niamey. Data were collected for socio demographic characteristics using a structured questionnaire. Samples were tested using ELISA and qRT-PCR for anti- HEV IgM and RNA detection respectively. HEV associated risk factors were determined using multivariate logistic regression models. Results: A total of 491 pregnant women were enrolled with mean age of 26.5 years. The prevalence of anti-HEV IgM antibodies was 17.1%, while HEV RNA was detected in 3.46% of participants, indicating recent and active HEV infection. Anti-HEV IgM seropositivity was more frequent among women aged 26-30 years and those in the third trimester of pregnancy. Gravidity was significantly associated with HEV RNA positivity (p = 0.032). In multivariable analysis, the use of well water was independently associated with HEV infection (aOR = 75.70; 95% CI: 1.23-4643.20; p = 0.039). Conclusion: In view of the high seroprevalence of HEV among pregnant women, preventive measures including hygiene sensitization should be prioritized. Further studies should be conducted to assess the real impact of HEV infection on maternal and fetal health.

Background and Aims: Hepatitis B virus (HBV) infection remains a significant global public health concern, particularly in developing countries, where it poses a major challenge to safe blood transfusion services. Blood donors represent an important subset of the population for assessing HBV prevalence, as transfusions are a key route for transmission. This study aimed to determine the seroprevalence of HBV infection among blood donors at Methodist Hospital, Wenchi, Ghana. Methods: A retrospective analysis was conducted using data from the blood bank at Methodist Hospital, Wenchi from January 2022 to December 2023 and analyzed using SPSS version 25. Results: The overall HBV seroprevalence among blood donors was 6.8%, with a higher infection rate among females (16.7%) compared to males (6.3%). The highest seroprevalence (9.4%) occurred in donors aged 30 to 39 years and voluntary donors showed a higher infection rate (8.2%) than non-voluntary donors (6.5%). Among blood groups, individuals with blood groups A and B exhibited the highest infection rates (8.5%). Factors such as age (AOR: 2.62, 95% CI: 1.10 to 5.32, p-value =0.023), gender (AOR: 2.10, 95% CI: 1.05 to 4.35, p-value= 0.004) and Rhesus status (AOR: 1.68, 95% CI: 1.08 to 3.35, p-value= 0.031) were significantly associated with HBV infection. Conclusion: The study revealed a significant HBV seroprevalence of 6.8% among blood donors, classifying the region as medium-endemic per WHO guidelines. The findings underscore the urgent need for enhanced HBV screening, rigorous blood safety measures and targeted public health interventions including vaccination and education campaigns to mitigate the transmission risk. Keywords: Hepatitis B virus, Blood donors, Seroprevalence, Seropositive, Ghana

Seasonal influenza remains a major cause of morbidity and mortality worldwide. Although neuraminidase inhibitors improve outcomes, influenza-related deaths persist. We evaluated the impact of early aspirin (ASA) and non-aspirin nonsteroidal anti-inflammatory drug (NSAID) use on outcomes in adults hospitalized with influenza. This retrospective study included adults admitted to the University of Minnesota Medical Center from 2016 to 2018. Continuous variables were summarized as medians with interquartile ranges (IQRs) and categorical variables as counts and percentages. Group comparisons used Wilcoxon rank-sum, Chi-square, or Fishers exact tests. Analyses included case-control comparisons, assessments by vaccination status, and subgroup analyses by early ASA or NSAID use. Among 2,816 patients, 320 had laboratory-confirmed influenza, with vaccination less common among cases. Unvaccinated patients had higher rates of intensive care unit (ICU) admission (23.6% vs. 11.1%; P = 0.003) and ventilatory support (15.0% vs. 6.1%; P = 0.009). In vaccinated patients, early ASA use was associated with older age and higher in-hospital mortality, whereas early NSAID use was associated with no in-hospital deaths, better one- and three-year survival (P < 0.001), and fewer, though not statistically significant, cardiovascular complications. In unvaccinated patients, ASA use was associated with lower three-year survival (59.1% vs. 79.2%; P = 0.013), while NSAID use was associated with fewer ICU admissions and no cardiovascular or renal complications. In both vaccinated and unvaccinated adults hospitalized with influenza, early NSAID use was associated with improved survival and fewer complications, whereas ASA use was associated with worse outcomes.

Background: Refractory and macrolide-resistant Mycoplasma pneumoniae pneumonia (MPP) has emerged as a major challenge in pediatric respiratory medicine, amplified by the post-2023 resurgence. However, a systematic overview of the research landscape specific to treatment-refractory and drugresistant disease in children remains lacking. Methods: Research articles and reviews on pediatric refractory or macrolide-resistant MPP published between 2000 and 2025 were retrieved from OpenAlex using Boolean searches. After screening, 2,286 records were quantitatively analyzed for annual output, contributing countries/institutions, thematic clusters, and citation-burst dynamics using Python. Results: Annual publications grew exponentially, with a pronounced surge after 2023 (n=378 in 2025). China produced the highest volume (45.1%) but recorded fewer citations per publication than the US, Japan, and Canada. The literature resolved into four clusters: macrolide resistance/molecular basis, epidemiology, etiology/co-infection, and refractory disease management. Burst analysis showed an evolution from earlier fronts like 23S rRNA mutations and azithromycin to recent emerging trends like pandemic-related co-circulation, genotype surveillance, and co-infection. Conclusions: Research on pediatric refractory and resistant MPP is expanding rapidly, shifting in emphasis from etiologic descriptions toward resistance mechanisms and clinical management. Standardizing the treatment of macrolide-unresponsive disease and post-pandemic epidemiological surveillance represent the principal directions for future work. Keywords: Mycoplasma pneumoniae; children; macrolide resistance; refractory pneumonia; bibliometric analysis; research trends

Excessive osteoclast activity contributes to pathological bone loss in osteoporosis, rheumatoid arthritis, and osteolytic malignancies. The effects of small catechol derivatives on receptor activator of nuclear factor-{kappa}B ligand (RANKL)-induced osteoclastogenesis remain poorly understood. This study investigated the effects of 4-methylcatechol (4-MC) on RANKL-induced NF-{kappa}B activation and osteoclast differentiation. 4-MC reduced RANKL-induced NF-{kappa}B luciferase activity in HEK-293T/RANK cells. 4-MC also suppressed RANKL-induced TRAP activity in RAW264.7 cells in a concentration-dependent manner and reduced the number of TRAP-positive multinucleated osteoclasts, without affecting cell viability. Molecular docking predicted non-covalent binding of 4-MC within the ATP-binding hinge region of IKK{beta} (PDB: 4KIK), forming a close polar contact with Glu97, predicted hydrogen bonds with Cys99, and a hydrophobic contact with Ile165, within the pocket occupied by the co-crystallized inhibitor K252a. Covalent docking predicted that the oxidized quinone form of 4-MC engages Cys179 in the IKK{beta} activation loop. Quantum chemical calculations confirmed a markedly higher electrophilicity index for the oxidized quinone than for the parent catechol, supporting this mechanism. In silico ADMET profiling indicated favorable drug-likeness and safety. These findings identify IKK{beta} as a plausible molecular target of 4-MC through both non-covalent and covalent mechanisms. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/741661v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@35a0d3org.highwire.dtl.DTLVardef@d19458org.highwire.dtl.DTLVardef@1623fadorg.highwire.dtl.DTLVardef@1429e8b_HPS_FORMAT_FIGEXP M_FIG C_FIG

Plant-derived small molecules possess highly diverse physicochemical properties, and the computational design of their protein recognition elements depends not only on the global structural quality of candidate backbones, but also on whether the local binding pocket, ligand-contact pattern, and predefined recognition conformation can be consistently retained after sequence design and structural back-prediction. To explore pocket-design strategies for different types of natural-product small molecules, this study selected capsaicin, (4R)-limonene, and quercetin as model ligands, representing a flexible amphipathic molecule, a compact hydrophobic monoterpene, and a rigid polyphenolic flavonoid scaffold, respectively, and covering the dimensions of pungent sensory flavor, volatile aroma, and flavonoid functional constituents. A ligand- physicochemical-property-guided computational design and multi-stage prioritization framework was established for candidate protein binders. The results showed that candidates with favorable initial global structural scores did not necessarily form reasonable local small-molecule binding pockets, indicating that evaluation of the local ligand environment is essential for candidate prioritization. After screening, 31 partial- pocket candidate backbones for capsaicin, 75 buried hydrophobic-pocket candidate backbones for (4R)-limonene, and 56 pocket-qualified candidate backbones for quercetin were obtained. Further sequence design and structural back-prediction analyses indicated that a subset of candidates could maintain the original pocket geometry and major ligand-contact patterns after sequence realization. Overall, these results suggest that the physicochemical properties of different plant-derived small molecules substantially influence the efficiency of de novo protein pocket formation, with compact hydrophobic ligands being more compatible with buried hydrophobic- pocket strategies, whereas flexible or multipolar ligands require a more refined balance between hydrophobic burial and polar exposure. This study provides a pre- experimental computational prioritization framework for natural-product small- molecule-recognizing proteins and offers candidate resources for subsequent protein expression, in vitro binding validation, active-constituent enrichment, and development of small-molecule biorecognition tools. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/743643v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@8fe6c2org.highwire.dtl.DTLVardef@176cef2org.highwire.dtl.DTLVardef@10c8201org.highwire.dtl.DTLVardef@2b28cf_HPS_FORMAT_FIGEXP M_FIG C_FIG