Immunity, Inflammation and Disease

Background: Oral dysbiosis has been associated with oral squamous cell carcinoma (OSCC); however, most microbiome studies rely on 16S ribosomal RNA (rRNA) gene sequencing, limiting species-level taxonomic resolution. Methods: Dental plaque, saliva, and tumor tissue samples from 10 patients with OSCC and dental plaque and saliva samples from 10 healthy controls were analyzed in this exploratory cross-sectional study. DNA was extracted and subjected to shotgun metagenomic sequencing using the Illumina MiSeq platform. Sequence reads were quality filtered with fastp, taxonomically classified using Kraken2 v2.1.3, and species-level abundances were re-estimated with Bracken v2.9 following the removal of human reads and low abundance taxa. Relative abundances were compared using the Mann Whitney U test with the Benjamini Hochberg false discovery rate correction, while the Bray Curtis principal coordinate analysis was used as an exploratory approach to visualize microbial community patterns. Results: Shotgun metagenomic sequencing revealed distinct bacterial community profiles across the oral microenvironment. Dental plaque exhibited the highest taxonomic diversity and relative abundance. The control plaque was enriched in Streptococcus koreensis, Capnocytophaga sp. oral taxon 878, Treponema sp. Marseille Q4132, and Leptotrichia sp. oral taxon 498, whereas the plaque from patients with OSCC showed a higher relative abundance of Pyramidobacter piscolens, Parvimonas parva, and Gemella sanguinis. Salivary samples displayed lower diversity and a more homogeneous composition, predominantly comprising Capnocytophaga endodontalis, Prevotella jejuni, Aggregatibacter aphrophilus, and Gemella sanguinis. The tumor tissue showed relatively higher abundance of Sellimonas catena, Escherichia coli, Solobacterium moorei, and Lacrimispora sp. HJ 01. Conclusions: This exploratory study provides species-level characterization of the oral microbiome across multiple oral microenvironments in OSCC and generates hypotheses for future integrative metagenomic and functional studies investigating the potential contribution of oral bacterial communities to OSCC pathogenesis.

Introduction Postoperative analgesic management after minimally invasive cardiac surgery (MICS) should facilitate early recovery while providing adequate pain control. However, direct evidence comparing postoperative remifentanil- and fentanyl-based analgesic strategies after MICS remains limited. We compared these strategies and explored their associations with postoperative recovery, postoperative nausea and vomiting (PONV), and pain management. Methods This retrospective single-center observational cohort study included patients who underwent MICS via a right mini-thoracotomy between January 2023 and June 2026. Patients were categorized according to postoperative remifentanil- or fentanyl-based analgesia in the intensive care unit. Outcomes included time to extubation, PONV, postoperative pain assessed using the numerical rating scale (NRS), additional analgesic use, and intensive care unit length of stay. Multivariable logistic regression examined the association between postoperative opioid strategy and PONV, adjusting for age, sex, and smoking history. Results PONV occurred less frequently in the remifentanil group than in the fentanyl group (20.6% vs 45.0%, P = 0.004), and this association remained significant after adjustment (adjusted odds ratio, 0.23; 95% confidence interval, 0.10-0.56; P = 0.001). Time to extubation was shorter with remifentanil (median, 179 [interquartile range, 134-240.5] vs 247 [190.2-276.5] min; P < 0.001). In contrast, NRS pain scores on postoperative day 0 were higher with remifentanil (3 [1-6] vs 1 [0-2]; P < 0.001), and additional analgesics were used more frequently (80.6% vs 33.3%; P < 0.001). Pain scores on postoperative day 1 did not differ significantly between groups. Conclusion Postoperative remifentanil-based analgesia after MICS was associated with less PONV and earlier extubation but also with greater early postoperative pain and more frequent additional analgesic use than fentanyl-based analgesia. Appropriate transition to longer-acting analgesics with multimodal analgesia may help preserve the potential benefits of remifentanil while maintaining adequate postoperative pain control.

BACKGROUND: Subarachnoid hemorrhage (SAH) induces inflammatory responses and subsequent immune cell activation, which may contribute in cerebral vasospasm, microcirculatory impairment and poor neurological outcomes. Although cerebral vasospasm has traditionally been considered a major cause of delayed cerebral ischemia after SAH, therapies targeting angiographic vasospasm have not consistently improved functional outcomes. Early inflammatory responses may contribute to microcirculatory impairment, cerebral vasospasm, and subsequent neurological injury. Herein, we investigated whether interleukin-10 (IL-10), an anti-inflammatory cytokine, improves these outcomes in an experimental SAH model. METHODS: Mice received intramuscular injections of either an adeno-associated virus encoding IL-10 (AAV/IL-10) vector or an AAV expressing green fluorescent protein (AAV/GFP) vector (control). India ink angiography was performed to assess the diameter of the sphenoidal segment of the middle cerebral artery (MCA), the total length of the visible cortical arteries, and cortical staining intensity, as indices of cerebral vasospasm, microcirculatory impairment, and cerebral perfusion, respectively. Perivascular inflammatory cell infiltration and cytokine levels were assessed using immunohistochemistry and ELISA. We also evaluated the therapeutic efficacy of the AAV/IL-10 vector when administered immediately after SAH induction. RESULTS: IL-10 overexpression significantly improved neurological outcomes after SAH and was associated with attenuated cerebral vasospasm and microcirculatory impairment, as well as preservation of cerebral perfusion. It also significantly reduced neutrophil and macrophage infiltration around the internal carotid artery and attenuated SAH-induced elevations in IL-6 and matrix metalloproteinase-3 levels. Mice treated with the AAV/IL-10 vector immediately after SAH induction showed significant improvements in neurological scores and cerebral perfusion. CONCLUSIONS: AAV-mediated IL-10 overexpression improves neurological outcomes after SAH, likely by attenuating inflammatory responses, cerebral vasospasm, and microcirculatory impairment. These findings suggest that IL-10-based anti-inflammatory therapy is a promising therapeutic strategy for SAH.

Background: Sickle cell anaemia (SCA) is characterised by chronic haemolysis, inflammation, platelet activation, and recurrent vaso-occlusive complications. Mean platelet volume (MPV) is a readily available platelet index, but evidence regarding its relationship with disease severity in paediatric SCA remains limited and inconsistent, particularly in African populations. Objective: To evaluate the relationship between MPV and disease severity among children with SCA in Kwara State, North-Central Nigeria. Methods: This hospital-based cross-sectional study included 51 clinically stable children with confirmed SCA consecutively recruited from the paediatric haematology clinic of Children Emergency Specialist Hospital, Ilorin. Complete blood count, including MPV, was performed using a Rayto RT-7600 automated haematology analyser. Disease severity was assessed using a composite clinical and laboratory scoring system based on a previously described method. Pearson's correlation, Spearman's rank correlation, simple linear regression, and the Kruskal-Wallis test were used as appropriate. Statistical significance was set at p < 0.05. Results: Of 51 participants, 14 (27.5%) had mild, 33 (64.7%) moderate, and 4 (7.8%) severe disease. Mean MPV was 9.34 +/- 0.76 fL (range, 8.0-11.2). Pearson's correlation showed a weak positive, non-significant linear relationship with severity score (r = 0.231, p = 0.103), whereas Spearman's analysis showed a weak positive monotonic association (rho = 0.286, p = 0.042). Regression explained 5.3% of severity-score variation (R2 = 0.053, p = 0.103). MPV did not differ significantly across severity categories (H = 2.163, p = 0.339). MPV correlated inversely with haemoglobin (r = -0.556, p < 0.001) and positively with platelet count (r = 0.307, p = 0.029). Conclusion: MPV showed a weak relationship with disease severity but inconsistent statistical evidence across analyses. The limited explained variance and absence of significant differences between severity categories do not support MPV as a standalone severity marker. Larger longitudinal studies are warranted. Keywords: Sickle cell anaemia; Mean platelet volume; Disease severity; Platelet indices; Paediatric haematology; Cross-sectional study; Nigeria.

Objective. To determine the publication rate of abstracts presented at the American Diabetes Association Scientific Sessions and to evaluate the association between statistical significance of study results and subsequent publication. Research Design and Methods. We conducted a retrospective cohort study of abstracts presented at the 2018 American Diabetes Association Scientific Sessions. The primary exposure was study result category (statistically significant vs. non-statistically significant findings), and the primary outcome was publication in an indexed journal within 5 years after conference presentation. Publication status was determined through PubMed/MEDLINE and Scopus searches. Adjusted relative risks (RRs) and 95% CIs were estimated using generalized linear models with Poisson distribution and robust variance. Results. Among 541 included abstracts, 321 (59.3%) were subsequently published in indexed journals. Abstracts reporting statistically significant findings had a higher publication rate than those reporting non-statistically significant findings (61.9% vs. 42.3%; p=0.002). In the adjusted analysis, abstracts with non-statistically significant findings had a lower likelihood of publication compared with those reporting statistically significant findings (adjusted RR 0.71 [95% CI 0.55-0.93]; p=0.013). Conclusions. Approximately four in ten abstracts presented at the ADA Scientific Sessions were not published within 5 years. Abstracts reporting non-statistically significant findings had a lower likelihood of subsequent publication, suggesting persistent publication bias in diabetology research. Future initiatives promoting the interpretation of effect estimates, confidence intervals and clinical relevance, rather than statistical significance alone, may help reduce selective dissemination of evidence

Background: Early trophic feeding promotes gut maturation, feeding tolerance, and growth in preterm neonates. However, delays remain common despite recommendations for initiation within 24 hours of birth, especially in resource-limited settings. Evidence on feeding initiation timing and predictors among Ethiopian preterm neonates is limited. Objective: To determine time to trophic feeding initiation and identify predictors among preterm neonates admitted to Adama Hospital Medical College, Ethiopia. Methods: A hospital-based retrospective cohort study was performed on 436 randomly chosen preterm neonates admitted to NICU. Data extraction was performed using a structured checklist. Time to trophic feeding initiation was analyzed using Kaplan-Meier estimates, log-rank tests, and bivariable and multivariable Cox regression models . Adjusted hazard ratios with 95% CIs were reported. Results:The sample comprised 416 preterm neonates, of whom 311 (74.8%) started trophic feeding during follow-up, and 105 (25.2%) were censored. The rate of initiation of trophic feeding was 1.92 per 100 person-hours (95% CI 1.72 to 2.15). Median time to initiation was 42 hours (interquartile range 24 to 50). Independent predictors of feeding initiation were determined by multivariable analysis and included gestational age, birth weight, maternal anaemia, respiratory distress syndrome and necrotising enterocolitis. Neonates born at 34-36 weeks had earlier initiation than those born at <34 weeks (AHR 1.39; 95 % CI 1.09 to 1.78). Similarly, neonates with a birth weight of [&ge;]1500 g had an earlier initiation than those with a birth weight of <1500 g (AHR 1.41; 95% CI 1.04 to 1.91). Delayed initiation was associated with maternal anaemia (AHR 0.70; 95% CI 0.51-0.95), respiratory distress syndrome (AHR 0.67; 95% CI 0.51-0.88) and necrotising enterocolitis (AHR 0.48; 95% CI 0.33-0.69). Conclusions: Delayed trophic feeding remains common among preterm neonates. Standardized feeding protocols, strengthened maternal care, and individualized nutrition strategies are needed to improve neonatal outcomes in study area.

Background: Serial glial fibrillary acidic protein (GFAP) trajectories have become an important framework for contextualizing evolving secondary-injury pathophysiology after moderate-to-severe traumatic brain injury (msTBI). However, total GFAP pools release and clearance signals that may be less useful for longitudinal bedside decisions than a proteoform-resolved assay. We compared total GFAP with neoGFAP, defined here as calpain-generated GFAP proteoforms intended to index active astroglial proteolysis during the subacute phase. Methods: We analyzed 651 serial serum samples from 95 msTBI patients from a previously described single-site cohort. Total GFAP and neoGFAP were measured on the same MSD platform from 6 to 240 hours after injury. Early (6 to 72 h) and late (96 to 240 h) windows, data-derived tertiles, and serial trajectory summaries were calculated directly from serial samples. Models were benchmarked against age plus admission post-resuscitation Glasgow Coma Scale (GCS) and the admission IMPACT extended risk score using five-fold stratified cross-validation. Outcomes were unfavorable outcome (GOSE 1 to 4), less-than-good recovery (GOSE 1 to 6), Disability Rating Scale (DRS) [&ge;]15, mortality, and neuroimaging worsening at 6 months. Results: The cohort contributed 95 serial biomarker profiles, with 90 participants evaluable for 6-month GOSE and 89 for DRS. Unfavorable outcome occurred in 57/90 (63.3%), and less-than-good recovery in 79/90 (87.8%). For unfavorable outcome, IMPACT plus early neoGFAP reached AUROC 0.85 versus 0.84 for IMPACT plus early total GFAP and 0.81 for IMPACT alone. For less-than-good recovery, IMPACT plus late neoGFAP achieved AUROC 0.90 versus 0.84 for late total GFAP and 0.82 for IMPACT alone. Secondary analyses for DRS, mortality, and neuroimaging worsening showed smaller differences. Conclusions: In this retrospective analysis, neoGFAP provided clearer incremental value than total GFAP for recovery-oriented monitoring, especially when late-window reassessment of patients who remained at risk for less-than-good recovery was required. Results support prospective testing of neoGFAP as a pathophysiology-informed adjunct to serial bedside decision making, repeat-assessment thresholds, and recovery stratification.

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

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.

Background: Patients receiving anti-TNF treatment for chronic inflammatory disease display impaired antibody responses, but it remains unclear how immune memory formation is affected. We evaluated antibody responses and memory B cells (Bmem) after COVID-19 booster vaccination in inflammatory bowel disease (IBD) patients receiving anti-TNF treatment. Methodology: Blood was sampled at baseline, 1, and 6 months after WH1/BA.5 bivalent or XBB.1.5 monovalent vaccination from 27 IBD patients receiving intravenous anti-TNF and 44 controls. Neutralizing antibodies were measured using an infectious virus assay. SARS-CoV-2 spike receptor binding domain (RBD)-specific serum IgG was quantified by ELISA, and RBD-specific Bmem were immunophenotyped by flow cytometry using recombinant proteins from ancestral, Omicron BA.1, BA.5, XBB.1.5, and JN.1 variants. Results: Serum IgG to vaccine RBD and neutralizing antibodies in patients increased pre to 1 month post-vaccination, but were lower than controls. Ancestral-, BA.5- and XBB.1.5-specific Bmem increased after vaccination but were significantly lower in patients than controls. Within RBD-specific Bmem, frequencies of recently activated CD21lo cells were increased after vaccination, and were higher in patients than controls. Fewer antigen-specific Bmem in patients expressed IgG4, and more expressed IgG3 or IgD following vaccination. Following vaccination, more RBD-specific Bmem recognized multiple viral variants. However, patients had fewer Bmem that could bind to subvariants than controls. Conclusion: Antibody and Bmem responses to COVID-19 booster vaccination in anti-TNF-treated IBD patients displayed reduced capacity, durability and cross-reactivity, suggesting impaired immune memory for protection against breakthrough infection. This supports the recommendation for annual booster vaccination to prevent severe disease and viral spread.

Background: Sleeve gastrectomy is the most frequently performed bariatric procedure worldwide but is associated with the development of de novo gastroesophageal reflux disease (GERD). Hiatal hernia has been identified as a relevant anatomical factor in postoperative reflux, although most studies evaluate it dichotomously without analyzing whether its size influences GERD risk. The aim was to evaluate the association between preoperative hiatal hernia size and de novo GERD after sleeve gastrectomy. Methods: Retrospective, single - center, observational study of patients undergoing sleeve gastrectomy at Hospital Central Norte de Petroleos Mexicanos (2018 - 2025). Demographic and clinical characteristics, endoscopic classification of hiatal hernia size (small <2 cm, medium 2.1 - 4 cm, large >4 cm), and evidence of de novo GERD were analyzed using descriptive statistics, Fisher's exact test, odds ratio (=R) estimation with 95% confidence intervals (CI), and binary logistic regression. Statistical significance was set at p<0.05. Results: Fiftysix patients were included (mean age 48.3 {+/-} 8.1 years; 67.9% male). Hiatal hernia classification was conclusive in 46 patients (82.1%): 63.0% no hernia, 4.3% small, 30.4% medium, and 2.2% large. De novo GERD occurred in 14.0% of patients without preexisting GERD (6/43). No significant association was found between hiatal hernia size and de novo GERD (Fisher p=0.515). In the reduced logistic model, neither hiatal hernia (medium/large vs. absent/small; OR 3.47; 95% CI 0.50 - 29.43; p=0.207) nor age (OR 1.02; 95% CI 0.90 - 1.13; p=0.754) was significantly associated. No evaluated factor (sex, smoking, alcohol, age) reached significance. Conclusions: In this cohort, no statistically significant association was demonstrated between preoperative hiatal hernia size and de novo GERD after sleeve gastrectomy; however, the low number of events limits the ability to exclude a clinically relevant association. These findings are compatible with a multifactorial mechanism rather than with the isolated presence of this finding. Prospective studies with larger sample sizes and standardized reflux assessment instruments are required to confirm these results.

Background & Aims: Fatigue is a central symptom of chronic liver disease (CLD), substantially impacting health-related quality of life (HRQoL). This study aimed to further understand CLD symptomatology, including fatigue, and its impact on HRQoL from a patient perspective. Methods: Abbott Global Assessment of Patients unmet needs (aGAP) was a multinational, cross-sectional survey in adults with compensated CLD in China, India and Mexico, conducted between July and November 2024. Adult participants who self-reported that they had physician-diagnosed CLD and were experiencing fatigue completed a quantitative survey to assess symptom burden and included three HRQoL patient-reported outcome (PRO) questionnaires (Patient-Reported Outcomes Measurement Information System [PROMIS]-29+2, Work Productivity and Activity Impairment - Specific Health Problem version 2.0 [WPAI: SHP], Multidimensional Fatigue Inventory [MFI]). Results: Overall, 505 participants (China: 200; Mexico: 105; India: 200) completed the study. Participants reported that their CLD-related fatigue sometimes, often or always affected their self-esteem/confidence (45.1%) and ability to maintain or acquire new employment (38.6%). Most participants reported moderate (51.3%) or serious (26.9%) fatigue, with 33.5% experiencing fatigue every day or almost every day. Many participants felt their social life was negatively impacted by their fatigue (47.3%) and that there were related financial difficulties (53.9%). Use of validated PRO tools demonstrated severe fatigue (MFI: overall mean [SD] 13.9 [3.4] general fatigue and 13.4 [3.6] physical fatigue) as well as substantial levels of work and activity impairment (WPAI: SHP overall mean [SD] 53.0 [26.4]) and high levels of anxiety, pain interference, depression and sleep interference (PROMIS T-scores [&ge;]54). Conclusions: Fatigue has a substantial impact on HRQoL among adults with CLD across several countries, highlighting a global unmet need for targeted interventions to effectively identify and manage the condition.

Purpose. Prognostic assessments after acute brain injury are largely narrative, and how prognostic language relates to subsequent care has not been measured at scale. We quantified where it is written and its association with a subsequent code-status limitation. Materials and Methods. Multidatabase observational study of adults with acute brain injury or a related neurologic emergency, using MIMIC-IV (2008-2019; discharge summaries and radiology reports) and a timestamped MIMIC-III cohort (notes and code-status orders). The exposure was documented prognostic language; outcomes were its association with a subsequent full-code-to-limitation transition, note-stream location, and completeness of documented command-following relative to structured Glasgow Coma Scale (GCS) motor scores. Results. Among 31,993 admissions (27,054 patients; median age, 69 years; 54.9% male), prognostic language in the timestamped cohort (MIMIC-III) was associated with a subsequent code-status limitation after multivariable adjustment (adjusted hazard ratio, 4.3; 95% CI, 2.9-6.5; unadjusted 14-day cumulative incidence, 40% vs 8.5%), including the comfort-measures component (3.9), a higher-risk subgroup (4.4), and after acute-physiology adjustment (4.1); the association was concentrated in the first 3 days. Non-prognostic severity language showed no comparable association (hazard ratios, 1.1-1.3). Prognostic language localized almost entirely to the narrative (4.9% of discharge summaries vs 0.015% of radiology reports); command-following was undocumented in 55.7% of summaries, and no final-24-hour GCS motor score was charted in 72.8%. Conclusions. Documented prognostic language after acute brain injury was written in the narrative, not structured fields, and was associated with a subsequent code-status limitation after multivariable adjustment. This observational association cannot establish causation but warrants prospective study.

Viral infections have long been proposed as environmental contributors to neurodegenerative diseases, including Parkinson's disease (PD), yet the molecular mechanisms linking infection and neurodegeneration are not well defined. Neuroinflammation and disruption of central nervous system (CNS) homeostasis have emerged as potential mediators. In this study, we used severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, as a model pathogen to investigate convergent molecular pathways between viral infection and PD. Single-nucleus RNA sequencing (snRNA-seq) was performed on post-mortem striatal tissue from 14 individuals stratified into four groups: COVID-19 only (COVID-19), PD only (PD), comorbid PD with COVID-19 (PD/COVID-19), and controls (Control). The PD/COVID-19 group exhibited an expanded astrocytic population and a pronounced interferon-associated molecular signature characterized by increased expression of canonical interferon-stimulated genes, including IFI44L (average log2FC= 3.9; adjusted p=2.3 x 10-373), IFI44 (average log2FC=2.9; adjusted p=8.0 x 10-266), ISG15 (average log2FC=3.1; adjusted p=1.2 x 10-197), and RSAD2 (average log2FC= 3.5; adjusted p=8.6 x 10-111). Pathway analyses demonstrated activation of innate immune and antiviral signaling pathways, particularly within microglia and astrocytes, including interferon signaling, pattern-recognition receptor pathways, and complement-associated responses. In parallel, genes involved in lipid metabolism, cholesterol homeostasis, synaptic maintenance, and neuronal signaling were reduced across disease groups. Proteomic analyses independently confirmed enrichment of antiviral and interferon-associated pathways and identified convergent suppression of sterol, cholesterol, and lipid metabolic processes. Our findings identify a convergent molecular signature linking PD and COVID-19, pronounced in comorbid individuals and characterized by interferon-driven innate immune activation, glial inflammatory responses, and dysregulation of lipid metabolic homeostasis. Collectively, the data support a model in which severe viral infection amplifies biological pathways already implicated in PD pathogenesis.

Background and Objectives: Preterm infants are commonly transfused, yet direct cardiorespiratory effects of red blood cell (RBC) transfusions remain poorly understood. We explored the feasibility of using multicentre electronic health data (EHD) to study such cardiorespiratory responses. Methods: Highly granular routine EHD were collected from preterm infants born <32 weeks gestational age at three European centres. Heart rate, oxygen saturation, and respiratory rate were evaluated 12 hours before and after the RBC transfusion. Results: A total of 321 transfusions in 164 infants were analysed. Overall, there was no significant change in the rate of bradycardia and apnoea following transfusion. Cardiorespiratory parameters varied substantially between infants; e.g. 20% of transfusions were associated with an unexpected, significant increase in heart rate. Respiratory rate and oxygen saturation exhibited similarly heterogenous patterns following transfusion. In sub-group analysis, the proportion of transfusions with increased heart rate was significantly higher within the first two weeks than later (32% vs 13%, p=0.0019). Conclusions: Multicentre EHD extraction allows to identify otherwise masked short-term effects of RBC transfusions on cardiorespiratory parameters, possibly indicating cardiac or pulmonary overload. Such effects may vary with adaptation to anaemia. Analysing EHD may ultimately enable personalized transfusion practice.

Background: Seasonal influenza, commonly known as flu, is an acute respiratory, highly contagious illness caused by influenza viruses. A clear understanding of influenza seasonality is crucial for guiding prevention and treatment strategies, including decisions on vaccination timing to prevent outbreaks. While well documented in temperate regions, data on influenza epidemiology in tropical areas, particularly sub-Saharan Africa, remain limited. We described the types, subtypes and positivity rate of seasonal influenza in Uganda during 2019-2023. Methods: We abstracted data from the National Influenza database on positive seasonal influenza cases confirmed by Polymerase Chain Reaction. The cases were disaggregated by age group, sex, region, month and year of reporting. Using Microsoft excel, we calculated the influenza positivity rate and disaggregated it by strain, sex, age, region and time. Test positivity rate was computed as the number of positive cases as a percentage of the total samples tested. Results: Among 17,957 individuals tested, the overall positivity rate for seasonal influenza was 5% (936 cases). Positivity was higher among males compared to females (7% vs. 4%), with children aged 5-9 years having the highest positivity rate (16%), while individuals aged 50-54 years had the lowest (1%). The median positivity rate was 4%, with a range of 1-16%. Regionally, the central region reported a positivity rate of 5%, with rates across all regions ranging from 5% to 8%. Over time, there was a gradual decline in positivity rates, decreasing from 16.5% in 2019 to 5.3% in 2023. Seasonal influenza exhibited bimodal peaks, with the primary peak occurring between March and May and a secondary peak from October to December. Influenza A was the predominant strain, accounting for 70% of seasonal influenza cases (669/936). Among the Influenza A subtypes, H3N2 was most common, representing 63% of cases (425/669). Conclusions: The declining seasonal influenza positivity rates from 2019 to 2023 and the predominance of Influenza A and H3N2 highlight the need for sustained surveillance in Uganda. Given Influenza A's high genetic variability and potential for novel strain emergence, monitoring circulating strains, informing vaccine development, and implementing targeted interventions for high-risk groups and regions are critical to controlling and preventing outbreaks.

The global dissemination of antimicrobial resistance is increasingly driven by bacterial clones combining antimicrobial resistance with enhanced virulence and environmental adaptability. Escherichia coli sequence type 131 (ST131) has historically been regarded as a major disseminator of the extended-spectrum {beta}-lactamase (ESBL) blaCTX-M-15. However, the emergence of E. coli ST1193 carrying blaCTX-M-15 may represent an ongoing shift in the epidemiology of this resistance determinant. Here, we investigated the prevalence, genomic characteristics, virulence and antimicrobial resistance potential of ST1193 in comparison with ST131. A total of 1,136 E. coli isolates were recovered from touristic and non-touristic environments, hospital-associated samples, and aircraft toilets in Guadeloupe. Isolates were whole-genome sequenced and analysed for antimicrobial resistance and virulence determinants. Additionally, publicly available genomic data comprising 1,215 blaCTX-M-15-positive ST131 and ST1193 isolates were analysed to assess temporal and geographical trends. ST1193 was significantly associated with aircraft-associated samples and exhibited a higher antimicrobial resistance gene burden than ST131, while maintaining a comparable virulence factor content. Analysis of publicly available genomes revealed similar temporal emergence patterns for blaCTX-M-15-positive ST1193 and ST131, with ST1193 showing a more recent distribution and a higher number of deposited isolates in recent years, consistent with a potential ongoing clonal replacement. Comparative genomic analysis identified numerous virulence and adaptation-associated genes shared between both sequence types, while ST1193 additionally carried distinct determinants, including components of the transmissible locus of stress tolerance. Furthermore, quinolone resistance-associated mutations were strongly linked to blaCTX-M-15 carriage, particularly among ST1193 isolates. Together, these findings identify E. coli ST1193 as an emerging high-risk clone with substantial potential for blaCTX-M-15 dissemination. Its association with aircraft-associated samples further highlights the potential role of air travel in long-distance transmission and underscores the need to reconsider current surveillance strategies focused predominantly on ST131.

Background and Objectives: Recurrence following burr-hole drainage of chronic subdural haematoma (cSDH) occurs in 10-25% of cases, sustained by neovascularisation of the subdural neomembrane supplied by the middle meningeal artery (MMA). MMA embolisation reduces recurrence; whether incidental burr-hole intersection of MMA branches during drainage confers similar benefit is unknown. Methods: We performed a multicentre retrospective cohort study of consecutive adults undergoing burr-hole drainage for cSDH at two UK tertiary neurosurgical centres. Postoperative thin-slice CT was used to classify burr-hole intersection of the underlying MMA groove (no hit, distal-branch hit or main-branch hit) and measure perpendicular burr-hole-to-MMA-groove distance. Co-primary outcomes were radiological recurrence and recurrence requiring intervention. Patient-clustered multivariable logistic regression adjusted for prespecified clinical covariates and treating site. Results: 227 patients (284 operated hemispheres) were included. Radiological recurrence decreased from 34.4% with no branch hit to 22.9% with main-branch intersection, with the gradient confined predominantly to unilateral cSDH. Main-branch intersection was associated with lower adjusted odds of radiological recurrence in unilateral cSDH (adjusted OR 0.30, 95% CI 0.11- 0.81; P = .018), with a similar but non-significant association in the overall cohort (adjusted OR 0.53, 95% CI 0.26-1.07; P = .075). Burr-hole-to-MMA-groove distance demonstrated a more consistent association: in the overall cohort, each 5-mm increase independently increased the odds of radiological recurrence (adjusted OR 1.38, 95% CI 1.04-1.82; P = .025). In unilateral cSDH, each 5-mm increase was independently associated with both radiological recurrence (adjusted OR 1.45, 95% CI 1.03-2.04; P = .034) and recurrence requiring intervention (adjusted OR 1.52, 95% CI 1.05-2.20; P = .027). Conclusion: Main-branch intersection of the middle meningeal artery during routine burr-hole surgery is associated with lower recurrence of unilateral cSDH, while the accompanying burr-hole-to-MMA-groove distance gradient provides biologically plausible support for a dose-response relationship. Together, these findings provide mechanistic rationale for prospective evaluation of intentional neuronavigation-guided MMA targeting (BURR-MMA; NCT07549893).

The 17th Ebola outbreak in the Democratic Republic of the Congo, announced on 15 May 2026, was attributed to Bundibugyo ebolavirus (BDBV). Although case isolation is the main control strategy, its effectiveness is compromised when patients escape isolation facilities before recovery. Between 14 May and 17 June 2026, 175 individuals reportedly left isolation facilities without formal discharge across Ituri Province. We assessed how this "isolation leakage" affects community transmission. We refined the SEIHFR framework to distinguish undetected community infections, detected but not-yet-isolated cases, isolated individuals, leakage, funeral-associated transmission, and removals. Using Bayesian inference, we fitted the model to daily Ituri surveillance data, escapee counts, and isolation census records. We estimated the leakage rate, reporting and detection probabilities, and the transmission rate, while fixing other parameters based on the BDBV literature. The model reproduced confirmed cases, deaths, discharges, and escapees. We estimated R_0=3.67 (95% HDI: 2.0-5.7), a leakage rate of {rho} {approx} 0.034 day^-1 (0.022-0.051), and high contact-tracing-driven detection (p_d {approx} 0.91-0.99). Leakage increased the detection-dependent reproduction number [R](p_d) from approximately 3.2 to above 5. Eliminating leakage reduced cumulative infections by about one-third, from 1,120 to 764, while the minimum detection level required for control increased from p_d [&ge;] 0.73 without leakage to p_d [&ge;] 0.87 at the fitted leakage rate. Shortening time to isolation prevented the most infections (73.4%; 59-84), followed by reducing leakage (29.7%; 14-52) and re-isolating escapees (12.6%; 6-24). Delaying leakage reduction until week 4 reduced its benefit from about 27% to below 2%. Isolation leakage represents a major transmission pathway that has until now gone largely unmeasured. While rapid initiation of isolation is highly beneficial, it cannot compensate for permeable isolation; therefore, early, community-driven efforts to control leakage, embedded within a multilayered response, are critical.

Background: In Tanzania, over 10,000 women aged 15-44 are diagnosed with cervical cancer annually, and more than 6525 die. The majority are diagnosed at an advanced stage, which contributes to delays in treatment enrollment and illness complications. Multiple factors can affect womens willingness and ability to access cervical pre-cancer screening. Purpose: To explore the barriers and facilitators to attending cervical pre-cancer screening among women living in a resource-constrained area of Southern Tanzania Methods: A qualitative study of 17 focus group discussions and 12 in-depth interviews was conducted from December 2023 to July 2024. Data collection took place in the community and health centers of a town and the surrounding rural areas in Kilombero district. The study used purposive sampling to recruit 112 women and 23 men aged 18- 50+ years. Results: Fear of death emerged as a central theme in the data, acting as both a barrier to and a facilitator of womens screening behavior. Women linked death with the screening procedure, receiving results and undergoing treatment. Participants mistrusted the speculum itself and linked it to pain, vaginal infection, and infertility. Conversely, fear of physical and social death motivated other women to attend the screening to learn about their health and prevent the consequences of a positive diagnosis. Public trust in the healthcare system and the role of health information sources were also identified as influencing women's decisions to undergo or not undergo screening. Conclusion: Our findings showed that cervical cancer screening uptake is influenced by fear of death and other co-factors. To improve early cervical cancer screening, programs and policy interventions are needed to raise awareness of the disease while also addressing womens specific concerns. Also, strengthening structural dimensions such as the availability of the healthcare workforce, healthcare facilities, and ensuring equitable service availability are essential to reducing cervical cancer complications and avoidable mortality.