Influenza A viruses (IAV) pose a persistent pandemic threat. Successful cross-species transmission from waterfowl to mammals requires host adaptation for efficient replication and spread. Avian IAVs are adapted to the temperature of the avian gut, approximately 41°C, while human IAVs replicate at 33°C in the upper respiratory tract. PB1, the catalytic core of the viral heterotrimeric RNA-dependent RNA polymerase (RdRp), is essential for viral RNA synthesis. Three pandemic IAV strains (1918, 1957, and 1968) carried an avian-origin PB1 gene, suggesting a selective advantage. Fever, a critical antiviral response, elevates body temperature to 38°C or higher and can restrict viral replication. We hypothesized that avian PB1 may allow IAV replication at febrile temperatures. Using a mini-replicon system, we demonstrate that a polymerase of a seasonal human H1N1 IAV fails to replicate viral RNA efficiently at 40°C, whereas substitution of the PB1 with that from the 1918, 1957, and 1968 pandemic viruses, or a low-pathogenic avian H2N1 virus, restores RNA synthesis. Chimeric seasonal human H1N1 viruses expressing avian or 1918 PB1 replicate at 40°C in MDCK cells, unlike wild-type H1N1. Activity assays with purified chimeric IAV polymerases further suggest that avian-origin PB1 may intrinsically enhance polymerase activity at elevated temperatures. Together, these data show that avian-origin PB1 enables IAV replication at febrile temperatures, highlighting its role in zoonotic emergence and host adaptation. Surveillance of avian-origin PB1 genes in IAVs circulating in mammals may help identify strains with pandemic potential and inform the development of countermeasures.IMPORTANCEInfluenza A viruses of avian origin remain a persistent threat to human health. The 1918, 1957, and 1968 pandemic influenza viruses each acquired an avian-origin PB1 gene, but the adaptive advantage conferred by these genes remains incompletely understood. Here, we show that avian-origin PB1 genes enhance viral RNA replication by a seasonal human influenza virus polymerase at elevated temperature and enable replication of a human influenza virus at 40°C, a temperature relevant to both avian hosts and human febrile illness. PB1-dependent effects were observed in cell-based polymerase assays, with purified polymerase, and during authentic virus infection. These findings identify temperature-resistant genome replication as a potential adaptive property of avian-origin PB1 and suggest that acquisition of an avian PB1 may help influenza viruses overcome temperature barriers encountered during adaptation to mammalian hosts.

Rheumatic heart disease (RHD) remains a leading cause of cardiovascular morbidity and mortality among pregnant women in resource-limited settings. Pregnancy induces significant hemodynamic changes that can decompensate pre-existing valvular heart disease, leading to life-threatening complications for both mother and fetus.

A 27-year-old pregnant woman (gravida 6, para 5) at approximately 34-38 weeks presented with progressive shortness of breath, palpitations. Based on the modified World Health Organization (mWHO) classification, she was categorized as Class IV (extremely high risk) bilateral lower limb swelling, cough, fatigue, and reduced appetite. Cardiovascular examination revealed a systolic murmur, loud S1 and S2, with bilateral basal crepitations on respiratory examination. Echocardiography demonstrated an enlarged left atrium (5 cm), moderate mitral stenosis, mild mitral regurgitation, with fixed mitral valve leaflets, pulmonary hypertension, poor right ventricular function, a large left atrial thrombus, Labor occurred spontaneously while on low-molecular-weight heparin (LMWH). Mild pericardial effusion, and preserved left ventricular ejection fraction (58%). Laboratory investigations showed elevated CRP (48.8 mg/L), thrombocytopenia (platelets 99 ×10⁹/L), mild coagulation abnormalities (INR 1.5), and urinalysis findings consistent with hematuria and proteinuria. Electrocardiography revealed sinus tachycardia, left atrial enlargement, right ventricular hypertrophy pattern, incomplete right bundle branch block, and prolonged QTc interval. The patient received multidisciplinary care including furosemide, metoprolol, and enoxaparin. She delivered a 2.1 kg neonate with good Apgar scores.

This case illustrates the severe maternal and fetal risks associated with advanced RHD during pregnancy. The presence of a large left atrial thrombus in a pregnant woman poses significant thromboembolic and hemodynamic risks. Multidisciplinary management involving cardiology, obstetrics, anesthesia, and intensive care is essential for optimizing outcomes.

This case highlights the critical importance of early recognition, strict adherence to CARE guidelines and multidisciplinary management, and the need for preventive strategies including primary prevention of rheumatic fever and secondary prophylaxis for RHD in resource-limited settings.

The U.S. Department of War (DOW)'s Global Emerging Infections Surveillance (GEIS) program conducts influenza surveillance within all geographic combatant commands to enhance U.S. force health protection and military readiness. This report compares laboratory-confirmed influenza data from the GEIS network with the World Health Organization (WHO) Global Influenza Surveillance and Response System (GISRS) from late 2025 through early 2026. Findings from the most recent 2025-2026 respiratory season show that while influenza trends were largely similar, with influenza A/H3N2 predominating, significant differences in percent positivity or subtype ratios emerged in Asia, East Africa, and South America. These discrepancies highlight the unique value of GEIS data, which fills critical surveillance gaps in strategic regions. This targeted surveillance provides crucial insights for mitigating infection risk to U.S. service members, informs annual vaccine strain selection, and ensures an early warning capability for emerging respiratory threats, directly supporting the readiness of the force.

Acute respiratory viral-bacterial co-infections complicate antimicrobial decisions because pathogen detection may not establish whether both organisms are clinically contributing to disease. We synthesized evidence from adult and pediatric acute respiratory infection cohorts, including influenza, SARS-CoV-2, respiratory syncytial virus, adenovirus, and selected mixed-detection febrile illness studies, to evaluate host-response biomarkers for distinguishing co-infection from mono-infection. Conventional C-reactive protein and procalcitonin were most useful as supportive or rule-out markers of bacterial involvement, but lacked sufficient specificity when used alone. Dual-axis strategies that combine antiviral and bacterial-response signals, including MxA/CRP, TRAIL/IP-10/CRP, CD169/CD64, IFI44L/FAM89A, and targeted transcriptomic or proteomic signatures, provided more biologically coherent discrimination of mixed infection states. These findings support prospective validation of integrated host-response panels as rapid decision-support tools for antimicrobial stewardship and clinically meaningful co-infection diagnosis.

Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity and mortality driven by dysregulated airway immunity. Macrophages and conventional type 2 dendritic cells (cDC2s) are central orchestrators of this process, yet their transcriptional heterogeneity at single-cell resolution and relationship to clinical severity remain incompletely characterized.

We performed integrative analysis of single-cell RNA sequencing (scRNA-seq) data from 45,708 lung immune cells combined with bulk microarray data from 236 lung tissue samples. After Harmony-based batch correction and graph-based clustering, 11 immune cell populations were annotated. Pseudobulk differential expression was performed using DESeq2, functional enrichment by gene set enrichment analysis against MSigDB Hallmark, KEGG, and GO:BP gene sets, and protein-protein interaction (PPI) network analysis using STRINGdb. Clinical correlation used Spearman rank correlation between hub gene expression and GOLD stage, FEV1% predicted, emphysema index, and DLCO%.

Macrophages were depleted in COPD while cDC2s were 4.7-fold expanded. Macrophages exhibited 1,268 differentially expressed genes dominated by IFN-γ response (NES = 2.60) and TNFα/NF-κB activation (NES = 2.41), with concurrent loss of mitochondrial function (NES = -2.40) and lysosomal acidification (NES = -2.25). cDC2s showed strong TNFα/NF-κB (NES = 2.88) and JAK-STAT (NES = 2.36) activation. PPI analysis identified IFNG, IL1B, CCR7, GZMB, and NFKB1 as central hubs. Cross-dataset validation confirmed LRG1, CCR7, IRF4, and TIMP1 as clinically correlated biomarkers.

This study identifies coordinated macrophage M1 polarization, metabolic dysfunction, and impaired efferocytosis in COPD, with cDC2-driven adaptive immune amplification. Eleven candidate biomarkers are proposed as targets for individualized nursing monitoring and precision respiratory care.

To investigate whether Notoginsenoside R1 (NG-R1) improves mitochondrial homeostasis by targeting the integrin signaling response (ISR) core transcription factor ATF4, thereby alleviating damage and apoptosis in asthma airway epithelial cells.

House dust mites (HDM) were used to establish an in vivo asthma mouse model and an in vitro BEAS-2B cell model. The anti-inflammatory and immunomodulatory effects of NG-R1 were evaluated through pulmonary function testing, bronchoalveolar lavage fluid (BALF) cell counting, and hematoxylin and eosin (H&E) staining. We evaluated the effects of NG-R1 on apoptosis and mitochondrial function using TUNEL, Annexin V-FITC/PI staining, transmission electron microscopy, MitoSox Red, TMRE, JC-1, and Western blot analysis of mitochondrial dynamics-related proteins (p-Drp1/Drp1, Mfn2, ATP5F1A). We used lentiviral knockdown of ATF4 combined with RNA-seq, GO enrichment analysis, and the STRING database to predict its downstream mechanisms. Molecular docking was used to predict the binding affinity between NG-R1 and ATF4, and the expression levels of ATF4, CHOP, and Bcl-2 were validated using Western blot analysis in both in vivo and in vitro models.

ATF4 expression was significantly elevated in lung tissue from asthmatic mice and in HDM-stimulated BEAS-2B cells, and was positively correlated with increased epithelial cell apoptosis and reduced migration and repair capacity. ATF4 knockdown alleviates HDM-induced increases in mitochondrial reactive oxygen species (ROS), decreases in membrane potential, mitochondrial ultrastructural damage, and disbalance in fission/fusion (downregulation of p-Drp1/Drp1 and upregulation of Mfn2 and ATP5F1A) via the ATF4-CHOP-Bcl2 signaling pathway, thereby inhibiting apoptosis. NG-R1 intervention significantly reduced airway hyperresponsiveness, total inflammatory cell counts in BALF, and levels of Th2 cytokines (IL-4, IL-13, IL-33) in asthmatic mice, and alleviated pulmonary inflammatory infiltration. Molecular docking and in vitro and in vivo experiments indicated that NG-R1 may specifically downregulate ATF4 (binding energies of -5.761 and -6.553 kcal/mol, respectively), modulate CHOP-Bcl2 expression levels, improve mitochondrial function and dynamic equilibrium, inhibit epithelial cell apoptosis, and promote migration and repair.

NG-R1 may regulate the ATF4-CHOP-Bcl2 signaling pathway by specifically binding to and downregulating ATF4, thereby alleviating mitochondrial stress-induced damage, inhibiting airway epithelial cell apoptosis, and promoting epithelial repair, suggesting that NG-R1 is a potential candidate drug for targeted asthma therapy.

BACKGROUND Kidney transplantation offers clear survival and quality-of-life advantages over dialysis, but severe pulmonary disease can complicate perioperative planning. In patients with substantially reduced respiratory reserve after pneumonectomy, general anesthesia may be considered high risk, creating uncertainty about transplant feasibility. CASE REPORT A 33-year-old man with end-stage kidney disease secondary to biopsy-proven AA amyloidosis was evaluated for preemptive living-donor kidney transplantation. He had undergone left pneumonectomy in 2015 because of bronchiectasis. Pulmonary function testing showed a mixed restrictive-obstructive pattern, with a forced vital capacity of 1.6 L (33% predicted), a forced expiratory volume in 1 second of 1.05 L (30% predicted), and a forced expiratory volume in 1 second/forced vital capacity ratio of 65%, indicating severe pulmonary impairment. Thoracic computed tomography demonstrated leftward mediastinal shift and diffuse bronchiectatic changes in the remaining right lung. Given the anticipated risk associated with general anesthesia, combined spinal-epidural anesthesia was selected. The transplant was successfully performed using a kidney from the patient's human leukocyte antigen (HLA)-identical sister. No intraoperative respiratory or hemodynamic instability occurred. Renal function rapidly improved after surgery: serum creatinine decreased from 6.6 mg/dL preoperatively to 0.63 mg/dL on postoperative day 3. Heavy proteinuria also greatly improved during follow-up. CONCLUSIONS This case demonstrates that kidney transplantation can be successfully performed under combined spinal-epidural anesthesia in carefully selected patients with severely limited pulmonary reserve after pneumonectomy. It also highlights the importance of individualized anesthetic planning and close multidisciplinary coordination for complex transplant candidates with major pulmonary comorbidities.

Leadless cardiac pacemakers (LPs) represent a significant advancement in cardiac pacing by eliminating the risks associated with traditional transvenous devices. Although single-chamber LPs have been in clinical use, the recent development of dual-chamber systems, such as AVEIR DR, offers synchronized atrial and ventricular pacing without the complications associated with transvenous hardware. Despite promising results, the widespread clinical adoption of dual-chamber LPs in Poland remains hindered by regulatory and reimbursement challenges. Although patients have access to single-chamber LPs, an unmet clinical need for dual-chamber LPs persists. Addressing this barrier is essential because dual-chamber LPs may optimize treatment by replacing two separate hospitalizations and implantations with a single procedure, thereby reducing the number of interventions and patient risk while lowering healthcare costs. This approach offers both clinical and economic benefits by improving efficiency and resource utilization in the healthcare system. This paper presents national experts' recommendations, supported by clinical research findings, on the use of dual-chamber LPs and solutions to increase their availability to patients in Poland.

To evaluate the adjusted associations and incremental prognostic value of admission white blood cell count (WBC) and neutrophil-to-lymphocyte ratio (NLR) for unfavorable discharge outcome after spontaneous intracerebral hemorrhage (sICH).

Consecutive adults with CT-confirmed sICH admitted to a tertiary academic hospital in northwestern China from August 2021 through August 2025 were retrospectively reviewed. After eligibility screening, 764 patients formed the study cohort. Admission WBC and log₂-transformed NLR were analyzed as continuous exposures; the primary outcome was discharge modified Rankin Scale (mRS) score ≥ 3. Multivariable models were benchmarked against the ICH score and a clinical severity model. Internal validation used 1000 bootstrap resamples. A three-level outcome-derived WBC-NLR burden classification was treated as exploratory and evaluated with 1000 nested bootstrap resamples.

The primary complete-case analysis included 752 patients, of whom 358 (47.6%) had an unfavorable discharge outcome. Each 1 × 10⁹/L increase in WBC was associated with higher odds of unfavorable outcome (adjusted odds ratio [OR], 1.116; 95% CI, 1.035-1.204; p = 0.004), and each doubling of NLR was associated with an adjusted OR of 2.187 (95% CI, 1.687-2.835; p < 0.001). Adding WBC and NLR increased the ICH score AUC from 0.757 to 0.848 (ΔAUC, 0.091; p < 0.001) and the clinical model AUC from 0.875 to 0.909 (ΔAUC, 0.034; p < 0.001). The optimism-corrected AUC of the full model was 0.900, with a corrected calibration slope of 0.932 and Brier score of 0.129. The nested-bootstrap-corrected AUC was 0.776 for the exploratory burden-only model and 0.899 after adding clinical covariates.

Admission WBC and NLR remained associated with unfavorable discharge outcome after adjustment and improved discrimination beyond established severity measures. They may support preliminary short-term risk assessment, whereas the outcome-derived burden categories require external validation. The discharge endpoint should not be interpreted as a substitute for 90-day functional outcome.

Atrial fibrillation (AF) is a common cardiac arrhythmia. Prevalence increases with age. It is a major public health concern due to high risk of thromboembolic complications such as stroke and systemic embolism. Direct oral anticoagulants (DOACs) have been shown to have improved safety and efficacy profiles and are the preferred therapy in all recent guidelines. However, patients are still discharged from internal medicine wards without appropriate DOAC therapy.

To investigate the effectiveness of hospitalization in correcting inappropriate therapy for AF in patients who were hospitalized in the internal medicine departments for any reason and discharged without receiving DOAC therapy.

In this retrospective cohort study, we gathered data from electronic medical records at Sheba Medical Center on 222 patients. The patients were divided into three groups based on the anticoagulation therapy they received.

The patient cohort (mean age of 77.1 years; 42.3% males; 21.6% presented with cognitive impairment. Researchers identified several potential contraindications for DOACs (renal disease in 24.3%, mechanical valves in 14.4%). When comparing patients with and without DOAC contraindications, there were no statistically significant differences regarding cognitive impairment rates or the lack of anticoagulation therapy. We further divided patients who did not receive DOACs into two groups: 134 due to contraindications and 88 mistakenly. Between these groups, baseline factors showed no statistically significant differences.

We found that older patients received less standardized care. Findings emphasize the need to consider individual patient characteristics and co-morbidities to eliminate management errors and improve the quality of clinical care.